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Montmorillonite (MMT) is an aluminosilicate clay with specific properties, such as improving growth performance and enhancing immunity. The effects of MMT supplements on performance, survival rate, body composition, haemolymph parameters, relative gene expressions, and antioxidant response of whiteleg shrimp (Litopenaeus vannamei) were investigated. Five diets with MMT supplementation were formulated at 0 (Control), 10 (MMT1), 20 (MMT2), 30 (MMT3) and 40 (MMT4) g/kg representing five treatments in replicates (15 tanks). A quadratic relation existed between the growth, feed conversion ratio, lysozyme and penaeidin3a and the MMT levels (further, MMT1 and MMT2 had significantly higher levels than other groups). Phenoloxidase, alkaline phosphatase and the expression of heat shock protein (HSP70), metallothionein and glutathione had linear relations so that MMT4 had a higher value than others (P < 0.05). Weight gain also had positive correlations with feed efficiency (correlation coefficient R: 0.76), HSP70 (R: 0.55), lysozyme (R: 0.72) and penaeidin3a (R: 0.60), while it had negative relations with daily feed intake, triglycerides and malondialdehyde. Malondialdehyde also had negative correlations with the level of MMT (R: − 0.69), weight gain (R: − 0.54), phenoloxidase (R: − 0.61), HSP70 (R: − 0.65), metallothionein (R: − 0.57) and catalase (R: 0.54) and also negative, but not significant, correlations with other measured parameters. In general, the findings of this study showed that the inclusion of MMT supplements in the diet improves the growth, antioxidant system and expression of genes related to whiteleg shrimp immunity and avoids lipid peroxidation. Most of the measured parameters suggest supplementing 20 g/kg MMT in diets of whiteleg shrimp, which is economically beneficial through improved growth and FCR. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a rare but severe form of psoriasis. However, the pathogenesis of GPP has not been fully elucidated. Although RNA-binding proteins (RBPs) and the alternative splicing (AS) process are essential for regulating post-transcriptional gene expression, their roles in GPP are still unclear. We aimed to elucidate the regulatory mechanisms to identify potential new therapeutic targets. Here, We analyzed an RNA sequencing (RNA-seq) dataset (GSE200977) of peripheral blood mononuclear cells (PBMCs) of 24 patients with GPP, psoriasis vulgaris (PV), and healthy controls (HCs) from the Gene Expression Omnibus (GEO) database. We found that the abnormal alternative splicing (AS) events associated with GPP were mainly “alt3p/alt5p”, and 15 AS genes were differentially expressed. Notably, the proportions of different immune cell types were correlated with the expression levels of regulatory alternatively spliced genes (RASGs): significant differences were observed in expression levels of DTD2, NDUFAF3, NBPF15, and FBLN7 in B cells and ARFIP1, IPO11, and RP11-326L24.9 in neutrophils in the GPP samples. Furthermore, We identified 32 differentially expressed RNA-binding proteins (RBPs) (18 up-regulated and 14 down-regulated). Co-expression networks between 14 pairs of differentially expressed RBPs and RASGs were subsequently constructed, demonstrating that these differentially expressed RBPs may affect the progression of GPP by regulating the AS of downstream immune/inflammatory-related genes such as LINC00989, ENC1 and MMP25-AS1. Our results were innovative in revealing the involvement of inflammation-related RBPs and RASGs in the development of GPP from the perspective of RBP-regulated AS. [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is a challenging condition with limited diagnostic and treatment options. In this study, we applied 12 distinct machine learning algorithms along with Non-negative Matrix Factorization (NMF) to analyze single-cell datasets from kidney biopsies, aiming to provide a comprehensive profile of LN. Through this analysis, we identified various immune cell populations and their roles in LN progression and constructed 102 machine learning-based immune-related gene (IRG) predictive models. The most effective models demonstrated high predictive accuracy, evidenced by Area Under the Curve (AUC) values, and were further validated in external cohorts. These models highlight six hub IRGs (CD14, CYBB, IFNGR1, IL1B, MSR1, and PLAUR) as key diagnostic markers for LN, showing remarkable diagnostic performance in both renal and peripheral blood cohorts, thus offering a novel approach for noninvasive LN diagnosis. Further clinical correlation analysis revealed that expressions of IFNGR1, PLAUR, and CYBB were negatively correlated with the glomerular filtration rate (GFR), while CYBB also positively correlated with proteinuria and serum creatinine levels, highlighting their roles in LN pathophysiology. Additionally, protein-protein interaction (PPI) analysis revealed significant networks involving hub IRGs, emphasizing the importance of the interleukin family and chemokines in LN pathogenesis. This study highlights the potential of integrating advanced genomic tools and machine learning algorithms to improve diagnosis and personalize management of complex autoimmune diseases like LN. [ABSTRACT FROM AUTHOR]

Introduction: The tumor microenvironment and IRGs are highly correlated with tumor occurrence, progression, and prognosis. However, their roles in grade II and III gliomas, termed LGGs in this study, remain to be fully elucidated. Our research aims to develop immune-related features for risk stratification and prognosis prediction in LGG. Methods: Using the ssGSEA method, we assessed the immune characteristics of the LGG population. We conducted differential analysis using LGG samples from the TCGA database and normal samples from GTEx, identifying 412 differentially expressed immune-related genes (DEIRGs). Subsequently, we utilized univariate Cox, LASSO, and multivariate Cox regression analyses to establish both a gene predictive model and a nomogram predictive model. Results: Here, we found that the ESTIMATE score, immune score and stromal score of high-immunity, high-grade and isocitrate dehydrogenase (IDH) wild-type glioma were higher than those of the corresponding group, and the tumor purity was lower. Higher ESTIMATE scores, stromal scores and immune scores indicated a poor prognosis in patients with LGG. Our four-gene prognostic model demonstrated superior accuracy compared to other molecular features. Validation using the CGGA as a testing set and the combined TCGA and CGGA cohort confirmed its robust prognostic value. Additionally, a nomogram integrating the prognostic model and clinical variables showed enhanced predictive capability. Discussion: Our study highlights the prognostic significance of the identified four DEIRGs (KLRC3, MR1, PDIA2, and RFXAP) in LGG patients. The predictive model and nomogram developed herein offer valuable tools for personalized treatment strategies in LGG. Future research should focus on further validating these findings and exploring the functional roles of these DEIRGs within the LGG tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN. Methods: We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB. LASSO regression, SVM-RFE, and random forest analysis identified four hub genes (EGF, PLTP, RGS2, PTGDS) as proficient predictors of DN. The model achieved an AUC of 0.995 and was validated on GSE142025. Single-cell RNA data (GSE183276) revealed increased hub gene expression in epithelial cells. CIBERSORT analysis showed differences in immune cell proportions between DN patients and controls, with the hub genes correlating positively with neutrophil infiltration. Molecular docking identified potential drugs: cysteamine, eltrombopag, and DMSO. And qPCR and western blot assays were used to confirm the expressions of the four hub genes. Results: Analysis found 95 and 88 distinctively expressed immune genes in the two DN datasets, with 14 consistently differentially expressed immune-related genes. After machine learning algorithms, EGF, PLTP, RGS2, PTGDS were identified as the immune-related hub genes associated with DN. In addition, the mRNA and protein levels of them were obviously elevated in HK-2 cells treated with glucose for 24 h, as well as their mRNA expressions in kidney tissues of mice with DN. Conclusion: This study identified 4 hub immune-related genes (EGF, PLTP, RGS2, PTGDS), as well as their expression profiles and the correlation with immune cell infiltration in DN. [ABSTRACT FROM AUTHOR]

This study aimed to develop a prognostic risk model based on immune-related long non-coding RNAs (lncRNAs). By analyzing the expression profiles of specific long non-coding RNAs, the objective was to construct a predictive model to accurately assess the survival prognosis of breast cancer (BC) patients. This effort seeks to provide personalized treatment strategies for patients and improve clinical outcomes. Based on the median risk value, 300 samples of triple-negative BC (TNBC) patients were rolled into a high-risk group (HR group, n = 140) and a low-risk group (LR group, n = 160). Multivariate Cox (MVC) analysis was performed by combining the patient risk score and clinical information to evaluate the prognostic value of the prognostic risk (PR) model. A total of 371 immune-related lncRNAs associated with the prognosis of TNBC were obtained from 300 TNBC samples. Nine associated with prognosis were obtained by univariate Cox (UVC) analysis, and 3 (AC090181.2, LINC01235, and LINC01943) were selected by MVC analysis for the construction of TNBC PR model. Survival analysis showed a great difference in TNBC patients in different groups (P < 0.001). The receiver operator characteristic (ROC) curve showed the model possessed a good area under ROC curve (AUC), which was 0.928. The patient RS jointing with clinical information as well as the MVC analysis revealed that RS was an independent risk factor (IRF) for prognosis of TNBC (P < 0.05, HR = 1.033286). Therefore, the lncRNAs associated with TNBC immunity can be screened by bioinformatics analysis, and the established PR model of TNBC could better predict the prognosis of patients with TNBC, exhibiting a high application value in clinic. [ABSTRACT FROM AUTHOR]

Protein hydrolysates as a feed supplement have been reported to enhance the growth of beneficial gut bacteria and improve the host's animal intestinal balance. Thus, this study evaluates the prebiotic effects of hydrolyzed squid by-products in black tiger shrimp, Penaeus monodon, diet. A 50-day feeding trial was conducted following a 4 × 2 factorial experiment in a completely randomized design. The juvenile P. monodon were fed plant-based diet (without fishmeal) supplemented with graded levels of 0, 0.5, 1.0, and 2.0% hydrolyzed squid by-products, either with or without Bacillus subtilis BF12. A control group fed a fish meal-based diet was also included. The shrimp growth, survival, nutrient retention, digestive enzyme activities, immune-related and gut pro-inflammatory gene expression, and intestine histomorphology were the evaluated biological responses. Feeding shrimp with plant-based diet containing 0.5% hydrolyzed squid by-products and B. subtilis BF12 supplement improved growth, enhanced feed conversion, improved nutrient retentions, upregulated the immune-related genes, and downregulated the gut pro-inflammatory genes. Enhanced digestive enzyme activities were observed in treatment groups with higher hydrolyzed squid by-product supplementation. Moreover, hydrolysate supplementation and probiotic application increased the shrimp's intestinal villi height and promoted the growth B. subtilis BF12 probiotics in the gut. Collectively, the present work suggests that hydrolyzed squid by-product protein supplementation at 0.5% and B. subtilis BF12 probiotics can promote growth, enhance the immunological responses, and improve the gut health of juvenile P. monodon fed a plant-based diet. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetic nephropathy (DN) is a major contributor to chronic kidney disease. This study aims to identify immune biomarkers and potential therapeutic drugs in DN. Methods We analyzed two DN microarray datasets (GSE96804 and GSE30528) for differentially expressed genes (DEGs) using the Limma package, overlapping them with immune-related genes from ImmPort and InnateDB. LASSO regression, SVM-RFE, and random forest analysis identified four hub genes (EGF, PLTP, RGS2, PTGDS) as proficient predictors of DN. The model achieved an AUC of 0.995 and was validated on GSE142025. Single-cell RNA data (GSE183276) revealed increased hub gene expression in epithelial cells. CIBERSORT analysis showed differences in immune cell proportions between DN patients and controls, with the hub genes correlating positively with neutrophil infiltration. Molecular docking identified potential drugs: cysteamine, eltrombopag, and DMSO. And qPCR and western blot assays were used to confirm the expressions of the four hub genes. Results Analysis found 95 and 88 distinctively expressed immune genes in the two DN datasets, with 14 consistently differentially expressed immune-related genes. After machine learning algorithms, EGF, PLTP, RGS2, PTGDS were identified as the immune-related hub genes associated with DN. In addition, the mRNA and protein levels of them were obviously elevated in HK-2 cells treated with glucose for 24 h, as well as their mRNA expressions in kidney tissues of mice with DN. Conclusion This study identified 4 hub immune-related genes (EGF, PLTP, RGS2, PTGDS), as well as their expression profiles and the correlation with immune cell infiltration in DN.

Abstract This study aimed to develop a prognostic risk model based on immune-related long non-coding RNAs (lncRNAs). By analyzing the expression profiles of specific long non-coding RNAs, the objective was to construct a predictive model to accurately assess the survival prognosis of breast cancer (BC) patients. This effort seeks to provide personalized treatment strategies for patients and improve clinical outcomes. Based on the median risk value, 300 samples of triple-negative BC (TNBC) patients were rolled into a high-risk group (HR group, n = 140) and a low-risk group (LR group, n = 160). Multivariate Cox (MVC) analysis was performed by combining the patient risk score and clinical information to evaluate the prognostic value of the prognostic risk (PR) model. A total of 371 immune-related lncRNAs associated with the prognosis of TNBC were obtained from 300 TNBC samples. Nine associated with prognosis were obtained by univariate Cox (UVC) analysis, and 3 (AC090181.2, LINC01235, and LINC01943) were selected by MVC analysis for the construction of TNBC PR model. Survival analysis showed a great difference in TNBC patients in different groups (P

Abstract Purpose Primary Sjogren's syndrome (pSS) is a prevalent autoimmune disease. The immune dysregulation it causes often leads to the development of diffuse large B-cell lymphoma (DLBCL) in clinical practice. However, how it contributes to these two disorders at the molecular level is not yet known. This study explored the potential molecular mechanisms associated with the differences between DLBCL and pSS. Patients and methods Gene expression matrices from discovery cohort 1, discovery cohort 2, and the validation cohort were downloaded from the GEO and TCGA databases. Weighted gene coexpression network analysis (WGCNA) was performed to identify the coexpression modules of DLBCL and pSS in discovery cohort 1 and obtain shared genes. GO and KEGG enrichment analyses and PPI network analysis were performed on the shared genes. Immune-related genes (IRGs) were intersected with shared genes to obtain common genes. Afterward, common genes were identified via machine learning methods. The immune infiltration analysis, miRNA-TF-hub gene regulatory chart, gene interactions of the hub genes, and gene‒drug target analysis were performed. Finally, STAT1 was identified as a possible essential gene by the above analysis, and immune infiltration and GSEA pathway analyses were performed in the high- and low-expression groups in discovery cohort 2. The diagnostic efficacy of the hub genes was assessed in the validation cohort, and clinical samples were collected for validation. Results By WGCNA, one modular gene in each group was considered highly associated with the disease, and we obtained 28 shared genes. Enrichment analysis revealed shared genes involved in the viral response and regulation. We obtained four hub genes (ISG20, STAT1, TLR7, and RSAD2) via the algorithm. Hub genes and similar genes are primarily involved in regulating type I IFNs. The construction of a miRNA-TF-hub gene regulatory chart revealed that hsa-mir-155-5p, hsa-mir-146b-5p, hsa-mir-21-3p, and hsa-mir-126-3p play essential roles in both diseases. Hub genes were differentially expressed in B-cell memory according to immune infiltration analysis. Hub genes had a strong diagnostic effect on both diseases. STAT1 plays an essential role in immune cells in both diseases. Conclusion We identified hub susceptibility genes for DLBCL and pSS and identified hub genes and potential therapeutic targets that may act as biomarkers.

Purpose: Primary Sjogren's syndrome (pSS) is a prevalent autoimmune disease. The immune dysregulation it causes often leads to the development of diffuse large B-cell lymphoma (DLBCL) in clinical practice. However, how it contributes to these two disorders at the molecular level is not yet known. This study explored the potential molecular mechanisms associated with the differences between DLBCL and pSS. Patients and methods: Gene expression matrices from discovery cohort 1, discovery cohort 2, and the validation cohort were downloaded from the GEO and TCGA databases. Weighted gene coexpression network analysis (WGCNA) was performed to identify the coexpression modules of DLBCL and pSS in discovery cohort 1 and obtain shared genes. GO and KEGG enrichment analyses and PPI network analysis were performed on the shared genes. Immune-related genes (IRGs) were intersected with shared genes to obtain common genes. Afterward, common genes were identified via machine learning methods. The immune infiltration analysis, miRNA-TF-hub gene regulatory chart, gene interactions of the hub genes, and gene‒drug target analysis were performed. Finally, STAT1 was identified as a possible essential gene by the above analysis, and immune infiltration and GSEA pathway analyses were performed in the high- and low-expression groups in discovery cohort 2. The diagnostic efficacy of the hub genes was assessed in the validation cohort, and clinical samples were collected for validation. Results: By WGCNA, one modular gene in each group was considered highly associated with the disease, and we obtained 28 shared genes. Enrichment analysis revealed shared genes involved in the viral response and regulation. We obtained four hub genes (ISG20, STAT1, TLR7, and RSAD2) via the algorithm. Hub genes and similar genes are primarily involved in regulating type I IFNs. The construction of a miRNA-TF-hub gene regulatory chart revealed that hsa-mir-155-5p, hsa-mir-146b-5p, hsa-mir-21-3p, and hsa-mir-126-3p play essential roles in both diseases. Hub genes were differentially expressed in B-cell memory according to immune infiltration analysis. Hub genes had a strong diagnostic effect on both diseases. STAT1 plays an essential role in immune cells in both diseases. Conclusion: We identified hub susceptibility genes for DLBCL and pSS and identified hub genes and potential therapeutic targets that may act as biomarkers. [ABSTRACT FROM AUTHOR]

A hyperactive tumour microenvironment (TME) drives unrestricted cancer cell survival, drug resistance, and metastasis in ovarian carcinoma (OC). However, therapeutic targets within the TME for OC remain elusive, and efficient methods to quantify TME activity are still limited. Herein, we employed an integrated bioinformatics approach to determine which immune-related genes (IRGs) modulate the TME and further assess their potential theragnostic (therapeutic + diagnostic) significance in OC progression. Using a robust approach, we developed a predictive risk model to retrospectively examine the clinicopathological parameters of OC patients from The Cancer Genome Atlas (TCGA) database. The validity of the prognostic model was confirmed with data from the International Cancer Genome Consortium (ICGC) cohort. Our approach identified nine IRGs, AKT2, FGF7, FOS, IL27RA, LRP1, OBP2A, PAEP, PDGFRA, and PI3, that form a prognostic model in OC progression, distinguishing patients with significantly better clinical outcomes in the low-risk group. We validated this model as an independent prognostic indicator and demonstrated enhanced prognostic significance when used alongside clinical nomograms for accurate prediction. Elevated LRP1 expression, which indicates poor prognosis in bladder cancer (BLCA), OC, low-grade gliomas (LGG), and glioblastoma (GBM), was also associated with immune infiltration in several other cancers. Significant correlations with immune checkpoint genes (ICGs) highlight the potential importance of LRP1 as a biomarker and therapeutic target. Furthermore, gene set enrichment analysis highlighted LRP1's involvement in metabolism-related pathways, supporting its prognostic and therapeutic relevance also in BLCA, OC, low-grade gliomas (LGG), GBM, kidney cancer, OC, BLCA, kidney renal clear cell carcinoma (KIRC), stomach adenocarcinoma (STAD), and stomach and oesophageal carcinoma (STES). Our study has generated a novel signature of nine IRGs within the TME across cancers, that could serve as potential prognostic predictors and provide a valuable resource to improve the prognosis of OC. [ABSTRACT FROM AUTHOR]

Despite considerable progress has been made in the understanding of the genetics and molecular biology of renal cell carcinoma (RCC), therapeutic options of patients with papillary renal cell carcinoma (PRCC) are limited. Immunotherapy based on immune checkpoint inhibitors (ICIs) has become a hot point in researching new drug for tumor and been tested in a number of human clinical trials. In this study, an immune-related gene prognostic index (IRGPI) was developed and provided a comprehensive and systematic analysis of distinct phenotypic and molecular portraits in the recognition, surveillance, and prognosis of PRCC. The reliability of the IRGPI was evaluated using independent datasets from GEO database and the expression levels of the genes in the IRGPI detected by real-time PCR. Collectively, the currently established IRGPI could be used as a potential biomarker to evaluate the response and efficacy of immunotherapy in PRCC. [ABSTRACT FROM AUTHOR]

Objective: Bioinformatics methods was used to develop and validate a prognostic risk model of pyroptosis and immune-related genes in hepatocellular carcinoma, and to explore immune correlated features based on the risk scores to guide personalised immunotherapy. Methods: TCGA-LIHC and GSE14520 gene expression profiles were downloaded from TCGA and GEO official websites respectively, and immune-related genes were downloaded from INNATEDB and IMMPORT websites. TCGA as the training group and GEO as the test group, Cox regression analysis was performed on expression profile of pyroptosis gene in training group. Selected prognostic related genes for consensus clustering, and extracted the intersection genes between difference genes and immune-related genes. Univariate Cox and Lasso regression analysis were applied to the intersection genes to obtain the prognosis related risk model. High- and low-risk groups were divided according to the median risk of training group, and the feasibility of model was verified by the test group. Finally, the enrichment analysis (GO, KEGG, GSEA), immune correlation analysis and model gene, protein expression of training group were discussed. Results:Nine reliable risk model genes were screened (ICAM1, S100P, FABP3, CCL20, HRG, IGHM, SPP1, C4BPA, C6). GO enrichment analysis showed that risk differential genes mainly existed in various metabolic processes. KEGG enrichment analysis showed that risk differential genes were mainly involved in complement and coagulation cascade signal pathways. CSEA showed that high-risk group was closely related to the activation of carcinogenic pathway. High- and low-risk groups have significant differences in immune infiltration, immune related pathways and immune checkpoints. HPA database showed that there were significant differences in immunohistochemical expression of ICAM1, S100P and SPP1 model genes. Conclusion: The risk model composed of 9 genes may become a potential biomarker related to the occurrence, development and prognosis of hepatocellular carcinoma, and provide new clues for optimizing the diagnosis and treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis. Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes' relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement. Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response's significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model. Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tongue squamous cell carcinoma (TSCC) represents one of the major subsets of head and neck cancer, which is characterized by unfavorable prognosis, frequent lymph node metastasis, and high mortality rate. The molecular events regulating tongue tumorigenesis remain elusive. In this study, we aimed to identify and evaluate immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in TSCC. METHODS: The lncRNA expression data for TSCC were obtained from The Cancer Genome Atlas (TCGA) and the immune-related genes were downloaded from the Immunology Database and Analysis Portal (ImmPort). Pearson correlation analysis was performed to identify immune-related lncRNAs. The TCGA TSCC patient cohort was randomly divided into training and testing cohorts. In the training cohort, univariate and multivariate Cox regression analyses were used to determining key immune-related lncRNAs, which were then validated through Cox regression analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) analysis in the testing cohort. RESULTS: Six immune-related signature lncRNAs (MIR4713HG, AC104088.1, LINC00534, NAALADL2-AS2, AC083967.1, FNDC1-IT1) were found to have prognostic value in TSCC. Multivariate and univariate cox regression analyses showed that the risk score based on our six-lncRNA model, when compared to other clinicopathological factors (age, gender, stage, N, T), was an important indicator of survival rate. In addition, Kaplan-Meier survival analysis demonstrated significantly higher overall survival in the low-risk patient group than the high-risk patient group within both training and testing cohorts. The ROC analysis indicated that the AUCs for 5-year overall survival were 0.790, 0.691, and 0.721, respectively, for training, testing, and entire cohorts. Finally, PCA analysis demonstrated that the high-risk and low-risk patient groups presented significant deviation regarding their immune status. CONCLUSIONS: A prognostic model based on six immune-related signature lncRNAs was established. This six-lncRNA prognostic model has clinical significance and may be helpful in the development of personalized immunotherapy strategies.

Background: The cabbage webworm, Hellula undalis (Fabricius) (Lepidoptera: Pyralidae), is a significant pest of brassicas and other cruciferous plants in warm regions worldwide. Transcriptome analysis is valuable for investigation of molecular mechanisms underlying the insect development and reproduction. De novo assembly is particularly useful for acquiring complete transcriptome information of insect species when there is no reference genome available. In case of Hellula undalis, only 17 nucleotide records are currently available throughout NCBI nucleotide database. Genes associated with metabolic processes, general development, reproduction, defense and functional genomics were not previously predicted in the Hellula undalis at the genomic level. Methods & Results: To address this issue, we constructed Hellula undalis transcriptome using Illumina NovaSeq6000 technology. Approximately 48 million 150 bp paired-end reads were obtained from sequencing. A total of 30,451 contigs were generated by de novo assembly of sample and were compared with the sequences in the NCBI non-redundant protein database (Nr). In total, 71 % of contigs were matched to known proteins in public databases including Nr, Gene Ontology (GO), and Cluster Orthologous Gene Database (COG), and then, contigs were mapped to 123 via functional annotation against the Kyoto Encyclopedia of Genes and Genomes pathway database (KEGG). In addition, we compared the ortholog gene family of the Hullula undalis, transcriptome to Spodoptera frugiperda, spodotera litura and spodoptera littoralis and found that 391 orthologous gene families are specific to Hullula undalis. A total of 1,913 potential SSRs was discovered in Hullula undalis contigs. Conclusions: This study is the first transcriptome data for Hullula undalis. Additionally, it serves as a valuable resource for identifying target genes and developing effective and environmentally friendly strategies for pest control.

Abstract The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.

Immune-modulating therapies exhibit abundant promise compared to traditional treatment for osteosarcoma. We aim to establish an immune-related prognostic signatures in osteosarcoma. We identified the differentially expressed genes in osteosarcoma compared with normal controls using the GEO dataset. The intersection with immune-related genes was considered as differentially expressed immune genes. Potential prognosis-related differentially expressed genes were first analyzed with the multifactor Cox regression and then the step function performed the iteration. The best model was finally chosen as the immunological risk score signature model. And finally, we evaluated the correlation of genes in the prognostic model with immune cells, common immune checkpoints, and immune checkpoint blockade responses. We identified 1527 significantly upregulated and 2407 significantly downregulated genes in osteosarcoma compared to normal samples. In the 258 differentially expressed immune genes, 20 genes with independent prognostic significance were included in the step function. Finally, we constructed a prognostic signature for overall survival based on five immune genes (JAG2, PLXNB1, CMKLR1, NUDT6, and PSMC4) in osteosarcoma. These five genes are closely related to immune infiltration. Osteosarcoma with high JAG2 expression or low CMKLR1 expression may be associated with better immune checkpoint blockade response. JAG2 overexpression or CMKLR1 inhibition induced sensitivity to PD-1 antibody in osteosarcoma cells. We constructed a prognosis prediction signature containing five immune-related genes (JAG2, PLXNB1, CMKLR1, NUDT6, and PSMC4) with a significant prognostic value in osteosarcoma. Significant differences in immune infiltration and immunotherapy responses were identified between groups with different levels of these genes. [ABSTRACT FROM AUTHOR]

Aeromonas veronii is widespread in aquatic environments and is responsible for infecting various aquatic animals. In this study, a dominant strain was isolated from the hepatopancreas of diseased Macrobrachium rosenbergii and was named JDM1-1. According to its morphological, physiological, and biochemical characteristics and molecular identification, isolate JDM1-1 was identified as A. veronii. The results of artificial challenge showed isolate JDM1-1 had high pathogenicity to M. rosenbergii with an LD50 value of 8.35 × 105 CFU/mL during the challenge test. Histopathological analysis revealed severe damage in the hepatopancreas and gills of the diseased prawns, characterized by the enlargement of the hepatic tubule lumen and gaps between the tubules as well as clubbing and degeneration observed at the distal end of the gill filament. Eight virulence-related genes, namely aer, ompA, lip, tapA, hlyA, flgA, flgM, and flgN, were screened by PCR assay. In addition, virulence factor detection showed that the JDM1-1 isolate produced lipase, lecithinase, gelatinase, and hemolysin. Furthermore, the mRNA expression profiles of immune-related genes of M. rosenbergii following A. veronii infection, including ALF1, ALF2, Crustin, C-lectin, and Lysozyme, were assessed, and the results revealed a significant upregulation in the hepatopancreas and intestines at different hours post infection. This study demonstrates that A. veronii is a causative agent associated with massive die-offs of M. rosenbergii and contributes valuable insights into the pathogenesis and host defense mechanisms of A. veronii invasion. [ABSTRACT FROM AUTHOR]

The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic kidney disease (DKD) is one of the prominent microvascular complications of diabetes and the leading cause of end-stage renal disease. Inflammation plays a crucial role in the development and progression of DKD. Currently, only a few studies depict the landscape of infiltrating immune cells and their potential regulatory network in DKD. To gain a better understanding of the role of immune cells in the renal microenvironment, we sought to reveal the profile of infiltrating immune cells and their potential regulatory network in DKD. Methods: We obtained the transcriptomes and the corresponding clinical data of 19 DKD and 25 control samples from the Gene Expression Omnibus and Nephroseq databases, respectively. Thereafter, we conducted an analysis on the infiltrating immune cells and identified immune-related differentially expressed genes through bioinformatics. Finally, correlation analyses among immune cells, immune genes, and clinical manifestations were performed, and differentially infiltrating immune cell subsets were verified through multiplex immunofluorescence staining. Results: We demonstrated the landscape of infiltrating immune cells in patients with DKD and identified the top five hub immune regulatory genes (C3, IL7R, TYROBP, BMP2, and CXCL6). Three of the core genes (C3, BMP2, and CXCL6) were significantly correlated with the estimated glomerular filtration rate. Through multiplex immunofluorescence staining, we verified that macrophage numbers were remarkably elevated, whereas Treg cells were remarkably reduced in diabetic kidney tissues. Th2 cells were scarce in the kidney tissue. Conclusion: Collectively, our findings shed light on new, possible therapeutic strategies for DKD, from an immune microenvironment perspective. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is one of the high‐risk pathogenic factors for colorectal cancer (CRC). However, the shared gene and signalling mechanisms between UC and CRC remain unclear. The goal of this study was to delve more into the probable causal relationship between UC and CRC. CRC and UC datasets were downloaded from the Gene Expression Omnibus database. Using R software and Perl, differentially expressed genes (DEGs) in both UC and CRC tissues were re‐annotated and screened. The biological activities and signalling pathways involved in DEGs were investigated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The STRING database and Cytoscape software were used to construct the gene interaction network. A total of 384 DEGs were selected for further investigation, and functional analysis revealed that inflammatory and immunological responses were crucial in the development of the two diseases. Moreover, the top 15 key genes involved in the UC and CRC were screened using cytoHubba, including IL1B, CXCL10, CCL20, MMP9, ICAM1, CCL4, CXCR1, MMP3, TLR2, PTGS2, IL1RN, IL6, COL1A2, TIMP1 and CXCL1. The identification of these genes in the present study may provide a novel perspective for the prediction, prevention and personalized medicine of UC and CRC patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze the pharmacological mechanism of sophora flavescens in the treatment of ulcerative colitis (UC) based on bioinformatics and molecular docking. METHODS: The ingredients target information of sophora flavescens was obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and related literature, the differential expression genes of UC were obtained by using the dataset (GSE206285) in the GEO database, the IRGs were collected through immune-related gene ( IRGs) database, and STRING platform was used to perform protein-protein interaction analysis, so as to screen the core targets of sophora flavescens in the treatment of UC through regulating the expression of IRGs. The enrichment analysis on related gene was conducted by using Metascape platform, and molecular docking verification was finally conducted on the main active ingredients and core targets in sophora flavescens. RESULTS: The potential active ingredients of sophora flavescens in the treatment of UC by regulating immune-related proteins were quercetin, luteolin, formononetin, 8-isoprenyl-kaempferol, phaseolin, wighteone, glyceollin, maackiain, kushenin and matrine; the core targets were matrix metalloproteinase (MMP) 9, interleukin (IL) 1β, CXC chemokine ligand 8 (CXCL8), PPARG, PTGS2 and IL-6; the involved signaling pathways were cancer-related pathway, lipid and atherosclerosis pathway, AGE-RAGE signaling pathway, IL-17 signaling pathway and tumor necrosis factor signaling pathway, etc. ; the binding energy of MMP9 to wighteone was -42. 7 kJ/ mol; the binding energy of PPARG to phaseolin was -41. 9 kJ/ mol; the binding energy of MMP9 to luteolin, PTGS2 to luteolin, PTGS2 to phaseolin and PTGS2 to glyceollin were -40. 6 kJ/ mol. CONCLUSIONS: This study has explored the potential mechanism of sophora flavescens in the treatment of UC by regulating IRGs, so as to provided a theoretical basis for the expansion of the clinical application of sophora flavescens and new therapeutic strategies for UC. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia, a severe pregnancy syndrome, is widely accepted divided into early‐ and late‐onset preeclampsia (EOPE and LOPE) based on the onset time of preeclampsia, with distinct pathophysiological origins. However, the molecular mechanism especially immune‐related mechanisms for EOPE and LOPE is currently obscure. In the present study, we focused on placental immune alterations between EOPE and LOPE and search for immune‐related biomarkers that could potentially serve as potential therapeutic targets through bioinformatic analysis. Methods: The gene expression profiling data was obtained from the Gene Expression Omnibus database. ESTIMATE algorithm and Gene Set Enrichment Analysis were employed to evaluate the immune status. The intersection of differentially expressed genes in GSE74341 series and immune‐related genes set screened differentially expressed immune‐related genes. Protein–protein interaction network and random forest were used to identify hub genes with a validation by a quantitative real‐time PCR. Kyoto Encyclopedia of Genes and Genomes pathways, Gene Ontology and gene set variation analysis were utilized to conduct biological function and pathway enrichment analyses. Single‐sample gene set enrichment analysis and CIBERSORTx tools were employed to calculate the immune cell infiltration score. Correlation analyses were evaluated by Pearson correlation analysis. Hub genes‐miRNA network was performed by the NetworkAnalyst online tool. Results: Immune score and stromal score were all lower in EOPE samples. The immune system‐related gene set was significantly downregulated in EOPE compared to LOPE samples. Four hub differentially expressed immune‐related genes (IL15, GZMB, IL1B and CXCL12) were identified based on a protein–protein interaction network and random forest. Quantitative real‐time polymerase chain reaction validated the lower expression levels of four hub genes in EOPE compared to LOPE samples. Immune cell infiltration analysis found that innate and adaptive immune cells were apparent lacking in EOPE samples compared to LOPE samples. Cytokine‐cytokine receptor, para‐inflammation, major histocompatibility complex class I and T cell co‐stimulation pathways were significantly deficient and highly correlated with hub genes. We constructed a hub genes‐miRNA regulatory network, revealing the correlation between hub genes and hsa‐miR‐374a‐5p, hsa‐miR‐203a‐3p, hsa‐miR‐128‐3p, hsa‐miR‐155‐3p, hsa‐miR‐129‐2‐3p and hsa‐miR‐7‐5p. Conclusions: The innate and adaptive immune systems were severely impaired in placentas of EOPE. Four immune‐related genes (IL15, GZMB, IL1B and CXCL12) were closely correlated with immune‐related pathogenesis of EOPE. The result of our study may provide a new basis for discriminating between EOPE and LOPE and acknowledging the role of the immune landscape in the eventual interference and tailored treatment of EOPE. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is a prevalent cause of death from malignant tumors. This study aimed to develop a nicotinamide adenine dinucleotide (NAD+) metabolism and immune-related prognostic signature, providing a theoretical foundation for prognosis and therapy in CRC patients. Methods: NAD + metabolism-related and immune-related subtypes of CRC patients were identified by consistent clustering. Differentially expressed genes (DEGs) between the two subtypes of CRC were identified by overlapping. A risk signature was constructed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Independent prognostic predictors were authenticated by Cox analysis. Gene set variation analysis (GSVA) and single-sample gene set enrichment analysis (ssGSEA) were applied to investigate the connection between the prognostic signature and the immune microenvironment. Chemotherapy drug sensitivity and immunotherapy responsiveness were projected using the ‘pRRophetic’ package and Tumor Immune Dysfunction and Exclusion (TIDE) website. The Human Protein Atlas (HPA) database was used to assess the protein expression of prognostic genes in CRC and normal tissues. Results: Using bioinformatics methods, three prognostic genes related to immune-related NAD + metabolism were identified, and the results were used to establish and verify a prognostic signature related to immune-related NAD + metabolism in CRC patients. Cox regression analysis confirmed that the risk score was a reliable independent prognostic predictor. GSVA and ssGSEA indicated that the prognostic signature was associated with the immune microenvironment. TIDE analysis suggested that the signature might act as an immunotherapy predictor. Chemotherapy sensitivity analysis revealed that COMP was correlated with chemotherapy sensitivity in CRC patients and might be a potential therapeutic target. Conclusion: This study identified NAD + metabolism-immune-related prognostic genes (MOGAT2, COMP, and DNASE1L3) and developed a prognostic signature for CRC prognosis, which is significant for clinical prognosis prediction and treatment strategy decisions for CRC patients.

Purpose: The development of tumor vaccines has become a hot topic in immunotherapy for osteosarcoma (OS); however, more tumor antigens with stronger immunogenicity need to be identified. Methods: We downloaded six sets of gene expression profile data from online databases. The overexpressed genes were analyzed, intersected, and used to calculate the immune infiltration abundance in the TARGET OS dataset based on their expression matrix. Potential tumor antigen genes were identified based on whether they exhibited a high correlation with the antigen-presenting cells (APCs). A total of 1330 immune-related genes (IRGs) from the ImmPort website were retrieved based on their expression, and the Consensus Cluster method was used to obtain immune subtypes of the OS samples. Prognosis, immune microenvironment, and sensitivity to drugs were compared among the immune subtypes. Results: In total, 680 genes were overexpressed in at least two datasets, of which TREM2, TNFRSF12A, and THY1 were positively correlated with different APCs. Based on the expression matrix of 1330 IRGs in TARGET-OS, two immune subtypes, IS1 and IS2, were identified. The prognosis of the IS1 subtype was better than that of IS2, the expression of immune checkpoint (ICP)-related genes was higher in patients with the IS1 subtype, and immune cell infiltration and sensitivity to 16 drugs were generally higher in IS1 subtype patients. Conclusion: We identified three APC-correlated genes that can be considered to code for potential novel tumor antigens for OS vaccines. Two immune subtypes in patients with OS were identified to implement personalized treatments using mRNA vaccines.

Peng Lu,1,2,&ast; Tun Wang,1,2,&ast; Zicheng Wan,1,2 Mo Wang,1,2 Yang Zhou,1,2 Zhenyu He,1,2 Sheng Liao,1,2 Haiyang Liu,3 Chang Shu1,2,4 1Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institute of Vascular Diseases, Central South University, Changsha, People’s Republic of China; 3Department of Geriatrics, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Center of Vascular Surgery, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chang Shu, Department of Vascular Surgery, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86 136 0744 4222, Email Shuchang@csu.edu.cnPurpose: Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but the low maturation rate is concerning. Immune cells’ impact on AVF maturation lacks bioinformatics research. The study aims to investigate the potential predictive role of immune-related genes and immune cell infiltration characteristics in AVF maturation.Patients and Methods: We analyzed the high-throughput sequencing dataset to identify differentially expressed genes (DEGs). Then, we performed enrichment analyses (GO, KEGG, GSEA) on immune-related genes and pathways in mature AVF. We focused on differentially expressed immune-related genes (DEIRGs) and constructed a PPI network to identify hub genes. These hub genes were validated in other databases and experiments, including qPCR and immunohistochemistry (IHC). The immune cell infiltration characteristics in native veins, failed AVFs, and matured AVFs were analyzed by cibersortX. Partial experimental validation was conducted using clinical samples.Results: Our results showed that immune-related genes and signaling pathways are significantly enriched in mature AVF. We validated this in other databases and ultimately identified three hub genes (IL1B, IL6, CXCR4) in combination with experiments. Significant differences in immune cell infiltration characteristics were observed among native veins, failed AVFs, and matured AVFs. Immune cell infiltration analysis revealed that accumulation of CD4+ T cells, dendritic cells, mast cells and M2 macrophages contribute to AVF maturation. These immune-related genes and immune cells have the potential to serve as predictive factors for AVF maturation. We partially validated this experimentally.Conclusion: From a bioinformatics perspective, our results have identified, for the first time, a set of immune-related genes and immune cell infiltration features that can characterize the maturation of AVF and significantly impact AVF maturation. These features hold potential as predictive indicators for AVF maturation outcomes.Keywords: AVF maturation, bioinformatics, immune-related genes, inflammation

Abstract Background Gastric cancer (GC) is a heterogeneous malignancy with variable clinical outcomes. The immune system has been implicated in GC development and progression, highlighting the importance of immune-related gene expression patterns and their prognostic significance. Objective This study aimed to identify differentially expressed immune-related genes (DEIRGs) and establish a prognostic index for GC patients using comprehensive bioinformatic analyses. Methods We integrated RNA sequencing data from multiple databases and identified DEIRGs by overlapping differentially expressed genes with immune-related genes. Functional enrichment analysis was performed to uncover the biological processes and signaling pathways associated with DEIRGs. We conducted a Weighted Gene Co-expression Network Analysis (WGCNA) to identify key gene modules related to with GC. Cox regression analysis was conducted to determine independent prognostic DEIRGs for overall survival prediction. Based on these findings, we developed an immune-related gene prognostic index (IRGPI) based on these findings. The prognostic value of the IRGPI was validated using survival analysis and an independent validation cohort. Functional enrichment analysis, gene mutation analysis, and immune cell profiling were performed to gain insights into the biological functions and immune characteristics associated with the IRGPI-based subgroups. Results We identified 493 DEIRGs significantly enriched in immune-related biological processes and signaling pathways associated with GC. WGCNA analysis revealed a significant module (turquoise module) associated with GC, revealing potential therapeutic targets. Cox regression analysis identified RNASE2, CGB5, CTLA4, and DUSP1 as independent prognostic DEIRGs. The IRGPI, incorporating the expression levels of these genes, demonstrated significant prognostic value in predicting overall survival. The IRGPI-based subgroups exhibited distinct biological functions, genetic alterations, and immune cell compositions. Conclusion Our study identified DEIRGs and established a prognostic index (IRGPI) for GC patients. The IRGPI exhibited promising prognostic potential and provided insights into GC tumor biology and immune characteristics. These findings have implications for guiding therapeutic strategies.

Jiaming He,1,2,&ast; Tiankuo Luan,3,&ast; Gang Zhao,4 Yingxue Yang5 1Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Institute of Life Sciences, Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3Department of Anatomy, Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Gastroenterology, Wushan County People’s Hospital of Chongqing, Chongqing, 404700, People’s Republic of China; 5Department of Gastroenterology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingxue Yang, Email yangyingxue@hospital.cqmu.edu.cnBackground: The objective is to create an IRGPI (Immune-related genes prognostic index), which could predict the survival and effectiveness of immune checkpoint inhibitor (ICI) treatment for lung adenocarcinoma (LUAD).Methods: By applying weighted gene co-expression network analysis (WGCNA), we ascertained 13 genes associated with immune functions. An IRGPI was constructed using four genes through multicox regression, and its validity was assessed in the GEO dataset. Next, we explored the immunological and molecular attributes and advantages of ICI treatment in subcategories delineated by IRGPI. The model genes were also validated by the random forest tree, and functional experiments were conducted to validate it.Results: The IRGPI relied on the genes CD79A, IL11, CTLA-4, and CD27. Individuals categorized as low-risk exhibited significantly improved overall survival in comparison to those classified as high-risk. Extensive findings indicated that the low-risk category exhibited associations with immune pathways, significant infiltration of CD8 T cells, M1 macrophages, and CD4 T cells, a reduced rate of gene mutations, and improved sensitivity to ICI therapy. Conversely, the higher-risk group displayed metabolic signals, elevated frequencies of TP53, KRAS, and KEAP1 mutations, escalated levels of NK cells, M0, and M2 macrophage infiltration, and a diminished response to ICI therapy. Additionally, our study unveiled that the downregulation of IL11 effectively impedes the proliferation and migration of lung carcinoma cells, while also inducing cell cycle arrest.Conclusion: IRGPI is a biomarker with significant potential for predicting the effectiveness of ICI treatment in LUAD patients and is closely related to the microenvironment and clinicopathological characteristics. Keywords: lung adenocarcinoma, immune-related genes, bioinformatics, prognostic index, IL11

Immune-related genes (IRGs) in hepatocellular carcinoma (HCC) are significantly associated with both tumor-infiltrating immune cells (TICs) and disease prognosis. Therefore, exploring the correlation between IRGs with HCC and its related mechanism will provide new evidence for the diagnosis and treatment of HCC. The current paper analyzed the TICs in 374 HCC samples retrieved from the TCGA-LIHC dataset using ssGSEA and divided them according to the level of immune cell. A total of 177 differentially expressed genes (DEGs) were analyzed by protein-protein interaction (PPI) networks and univariate and multivariate Cox regression analyses. Four IRGs (C7, CTSV, MMP1, and VCAN) were found to be indicators of the immune prognosis for HCC according to the PPI network and Cox regression analyses of 177 DEGs, which was independently validated using an external dataset. A prognosis risk model was constructed for factors dependent on the four IRGs. Prognostic risk was associated with the subtype of infiltrating immune cells. Four effective IRGs were identified as novel independent prognostic factors that were correlated with tumor immune infiltration in HCC. This signature may guide the choice of immunotherapy for HCC. [ABSTRACT FROM AUTHOR]

The main objective of the current trial was to evaluate the beneficial influences of Origanum vulgare leaf extract (OVLE) on growth, some blood indices, redox status, and the expression of some growth and immune-related genes. Three thousand seven hundred and eighty Nile tilapia fingerlings were allocated to six equal groups. The first group served as a control and received a basal diet, while the other five groups were fed diets containing graded amounts of OVLE (0.1, 0.2, 0.3, 0.4, and 0.5%, respectively) and defined as OVLE0.1, OVLE0.2, OVLE0.3, OVLE0.4, and OVLE0.5 for 98 days. Growth performance and feed efficiency parameters were significantly improved in OVLE0.4 and OVLE0.5 groups compared with the control group. The hematological indices, specifically hemoglobin, red blood cell, and white blood cell count were significantly increased in the fish group fed a 4% OVLE-supplemented diet compared to other groups. Fish fed higher dietary inclusion levels of OVLE significantly increased total protein and albumin concentrations compared to other experimental groups. The OVLE0.4 and OVLE0.5 supplemented groups promoted innate immune response and phagocytic activity and stimulated the lipase enzyme activity of Nile tilapia. All estimated redox markers were significantly improved in the fish groups that received 4 or 5% OVLE compared with the control and other OVLE groups. The fish groups fed higher levels of OVLE significantly upregulated the expression of GH, IL-8, and IL-1β genes and downregulated the expression of the Hsp70 gene. Furthermore, the intestinal histological features demonstrated normal structure in all OVLE-administered fish groups, with improved intestinal villus length compared to the untreated group. Finally, it could be concluded that including OVLE in the Nile tilapia diet at higher levels (0.4 up to 0.5%) could improve performance and general health status. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demyelinating lesions in the white matter of the central nervous system. Studies have shown that exercise is beneficial for multiple sclerosis (MS). However, the molecular basis is largely unknown. Materials and Methods: We integrated multiple blood and hippocampus transcriptome data from subjects with physical activity or MS. Transcription change associations between physical activity and MS were analyzed with bioinformatic methods including GSEA (Gene Set Enrichment Analysis) and GO (Gene Ontology) analysis. Results: We find that exercise can specifically reverse immune-related genes in the hippocampus of MS patients, while this effect is not observable in blood. Moreover, many of these reversed genes encode immune-related receptors. Interestingly, higher levels of physical activity have more pronounced effects on the reversal of MS-related transcripts. Conclusions: The immune-response related genes or pathways in the hippocampus may be the targets of exercise in alleviating MS conditions, which may offer new therapeutic clues for MS. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) appears to be strongly associated with immune-related genes. However, immune-related genes are not well understood as a prognostic marker in HCC caused by the hepatitis B virus (HBV). The purpose of this study was to investigate the prognostic significance of immune-related genes in HBV-infected HCC. Methods: Gene expression data from 114 HBV-infected HCC and 50 normal tissues were integrated into The Cancer Genome Atlas. Differentially expressed immune-associated genes were analyzed to identify immune-associated differential genes associated with overall survival. Least Absolute Shrinkage and Selection Operator and multivariate Cox regressions were used to constructing immunoprognostic models. An independent prognostic factor analysis using multiple Cox regressions was also performed for HBV-infected HCCs. Immunocorrelation analysis markers and immune cell infiltration were also investigated. Results: We found 113 differentially expressed immune-associated genes. Immune-related differential genes were significantly correlated with the overall survival of HCC patients. We constructed an immune-based prognostic model using multivariate Cox regression analysis including seven immune-related genes. According to further analysis, immune-related prognostic factors may serve as independent prognostic indicators in the clinical setting. There is also evidence that the 7-gene prognostic model reflects the tumor immune microenvironment as a result of the risk score model and immune cell infiltration. Conclusions: As a result of our study, we screened immune-related genes for prognosis in HBV-infected HCC and developed a novel immune-based prognostic model. The research not only provides new prognostic biomarkers but also offers insight into the tumor immune microenvironment and lays the theoretical groundwork for immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is a heterogeneous malignancy with variable clinical outcomes. The immune system has been implicated in GC development and progression, highlighting the importance of immune-related gene expression patterns and their prognostic significance. Objective: This study aimed to identify differentially expressed immune-related genes (DEIRGs) and establish a prognostic index for GC patients using comprehensive bioinformatic analyses. Methods: We integrated RNA sequencing data from multiple databases and identified DEIRGs by overlapping differentially expressed genes with immune-related genes. Functional enrichment analysis was performed to uncover the biological processes and signaling pathways associated with DEIRGs. We conducted a Weighted Gene Co-expression Network Analysis (WGCNA) to identify key gene modules related to with GC. Cox regression analysis was conducted to determine independent prognostic DEIRGs for overall survival prediction. Based on these findings, we developed an immune-related gene prognostic index (IRGPI) based on these findings. The prognostic value of the IRGPI was validated using survival analysis and an independent validation cohort. Functional enrichment analysis, gene mutation analysis, and immune cell profiling were performed to gain insights into the biological functions and immune characteristics associated with the IRGPI-based subgroups. Results: We identified 493 DEIRGs significantly enriched in immune-related biological processes and signaling pathways associated with GC. WGCNA analysis revealed a significant module (turquoise module) associated with GC, revealing potential therapeutic targets. Cox regression analysis identified RNASE2, CGB5, CTLA4, and DUSP1 as independent prognostic DEIRGs. The IRGPI, incorporating the expression levels of these genes, demonstrated significant prognostic value in predicting overall survival. The IRGPI-based subgroups exhibited distinct biological functions, genetic alterations, and immune cell compositions. Conclusion: Our study identified DEIRGs and established a prognostic index (IRGPI) for GC patients. The IRGPI exhibited promising prognostic potential and provided insights into GC tumor biology and immune characteristics. These findings have implications for guiding therapeutic strategies. [ABSTRACT FROM AUTHOR]

The role of sugarcane bagasse (SCB) as a cheap carbohydrate (CHO) source was evaluated in L. vannamei larvae on the zootechnical indices and the countenance of growth, immune and antioxident genes in the liver and muscle tissues. The experiment includes two treatments, the control which feeds a commercial diet and the SCB treatment. It continued for 45 days in outside ponds in ternary (each supplied with six hundred shrimp larvae). The results revealed that both growth and survival rates of SCB treatment were significantly improved (P < 0.05) when versus to the basal. The hepatic (H) and muscular (M) genes expression increased considerably in the SCB treatment (P ≤ 0.05) versus control. The SCB treatment was the highest in all mRNA transcripts of studied immune-related genes. The expression of antioxidant genes superoxide destmutase (SOD) and glutathione peroxidase (GPx) in both H and M were increased significantly in SCB treatment relative to the control. Generally, the results highlight the importance of inclusion SCB in a zero water exchange system without an artificial diet ameliorates both zootechnical and immunity in L. vannamei.

Objective: This study aimed to investigate the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and examine its impact on macrophage M2 polarization using the TCGA and GEO databases. Methods: By combining TCGA and GEO databases, differential gene expression between CRC samples and standard tissue samples was analyzed to screen for immune-related genes (IRGs) associated with the prognosis of CRC patients. A predictive risk model was constructed based on 18 key IRGs, which were then validated using the GEO dataset. The relationship between transcription factors and IRGs was further explored to investigate their regulatory network in CRC. In vivo and in vitro experiments were carried out to validate these regulatory relationships and explore the function of SPDEF and CCL28 in CRC. Results: Twelve key IRGs associated with clinical and pathological characteristics of CRC patients were identified. Among them, CCL28 significantly impacted macrophage infiltration in CRC cells and may be a critical factor in immune evasion. In both in vitro and in vivo experiments, overexpression of SPDEF upregulated CCL28 expression, thereby suppressing M2 polarization of macrophages and inhibiting CRC cell proliferation and tumor growth. Notably, interference with CCL28 could reverse the effect of SPDEF overexpression. Conclusion: SPDEF can suppress immune evasion of CRC cells by activating CCL28, which is achieved through the modulation of M2 polarization of macrophages. This provides a new research direction and potential therapeutic target for immunotherapy in CRC.

Abstract Background The immune system played a multifaceted role in ovarian cancer (OC) and was a significant mediator of ovarian carcinogenesis. Various immune cells and immune gene products played an integrated role in ovarian cancer (OC) progression, proved the significance of the immune microenvironment in prognosis. Therefore, we aimed to establish and validate an immune gene prognostic signature for OC patients’ prognosis prediction. Methods Differently expressed Immune-related genes (DEIRGs) were identified in 428 OC and 77 normal ovary tissue specimens from 9 independent GEO datasets. The Cancer Genome Atlas (TCGA) cohort was used as a training cohort, Univariate Cox analysis was used to identify prognostic DEIRGs in TCGA cohort. Then, an immune gene-based risk model for prognosis prediction was constructed using the LASSO regression analysis, and validated the accuracy and stability of the model in 374 and 93 OC patients in TCGA training cohort and International Cancer Genome Consortium (ICGC) validation cohort respectively. Finally, the correlation among risk score model, clinicopathological parameters, and immune cell infiltration were analyzed. Results Five DEIRGs were identified to establish the immune gene signature and divided OC patients into the low- and high-risk groups. In TCGA and ICGC datasets, patients in the low-risk group showed a substantially higher survival rate than high-risk group. Receiver operating characteristic (ROC) curves, t-distributed stochastic neighbor embedding (t-SNE) analysis and principal component analysis (PCA) showed the good performance of the risk model. Clinicopathological correlation analysis proved the risk score model could serve as an independent prognostic factor in 2 independent datasets. Conclusions The prognostic model based on immune-related genes can function as a superior prognostic indicator for OC patients, which could provide evidence for individualized treatment and clinical decision making.

Abstract Background Sepsis is a high mortality disease which seriously threatens human life and health, for which the pathogenetic mechanism still unclear. There is increasing evidence showed that immune and inflammation responses are key players in the development of sepsis pathology. LncRNAs, which act as ceRNAs, have critical roles in various diseases. However, the regulatory roles of ceRNA in the immunopathogenesis of sepsis have not yet been elucidated. Results In this study, we aimed to identify immune biomarkers associated with sepsis. We first generated a global immune-associated ceRNA (IMCE) network based on data describing interactions pairs of gene–miRNA and miRNA–lncRNA. Afterward, we excavated a dysregulated sepsis immune-associated ceRNA (SPIMC) network from the global IMCE network by means of a multi-step computational approach. Functional enrichment indicated that lncRNAs in SPIMC network have pivotal roles in the immune mechanism underlying sepsis. Subsequently, we identified module and hub genes (CD4 and STAT4) via construction of a sepsis immune-related PPI network. Then, we identified hub genes based on the modular structure of PPI network and generated a ceRNA subnetwork to analyze key lncRNAs associated with sepsis. Finally, 6 lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) that identified as immune biomarkers of sepsis. Moreover, the CIBERSORT algorithm and the infiltration of circulating immune cells types were performed to identify the inflammatory state of sepsis. Correlation analyses between immune cells and sepsis immune biomarkers showed that the LINC00265 was strongly positive correlated with the macrophages M2 (r = 0.77). Conclusion Collectively, these results may suggest that these lncRNAs (LINC00265, LINC00893, NDUFA6-AS1, NOP14-AS1, PRKCQ-AS1 and ZNF674-AS1) played important roles in the immune pathogenesis of sepsis and provide potential therapeutic targets for further researches on immune therapy treatment in patients with sepsis.

Abstract Background As one of the most common intestinal inflammatory diseases, celiac disease (CD) is typically characterized by an autoimmune disorder resulting from ingesting gluten proteins. Although the incidence and prevalence of CD have increased over time, the diagnostic methods and treatment options are still limited. Therefore, it is urgent to investigate the potential biomarkers and targeted drugs for CD. Methods Gene expression data was downloaded from GEO datasets. Differential gene expression analysis was performed to identify the dysregulated immune-related genes. Multiple machine algorithms, including randomForest, SVM-RFE, and LASSO, were used to select the hub immune-related genes (HIGs). The immune-related genes score (IG score) and artificial neural network (ANN) were constructed based on HIGs. Potential drugs targeting HIGs were identified by using the Enrichr platform and molecular docking method. Results We identified the dysregulated immune-related genes at a genome-wide level and demonstrated their roles in CD-related immune pathways. The hub genes (MR1, CCL25, and TNFSF13B) were further screened by integrating several machine algorithms. Meanwhile, the CD patients were divided into distinct subtypes with either high- or low-immunoactivity using single-sample gene set enrichment analysis (ssGSEA) and consensus clustering. By constructing IG score based on HIGs, we found that patients with high IG score were mainly attributed to high-immunoactivity subgroups, which suggested a strong link between HIGs and immunoactivity of CD patients. In addition, the novel constructed ANN model showed the sound diagnostic ability of HIGs. Mechanistically, we validated that the HIGs play pivotal roles in regulating CD's immune and inflammatory state. Through targeting the HIGs, we also found potential drugs for anti-CD treatment by using the Enrichr platform and molecular docking method. Conclusions This study unveils the HIGs and elucidates the networks regulated by these genes in the context of CD. It underscores the pivotal significance of HIGs in accurately predicting the presence or absence of CD in patients. Consequently, this research offers promising prospects for the development of diagnostic biomarkers and therapeutic targets for CD.

A hyperactive tumour microenvironment (TME) drives unrestricted cancer cell survival, drug resistance, and metastasis in ovarian carcinoma (OC). However, therapeutic targets within the TME for OC remain elusive, and efficient methods to quantify TME activity are still limited. Herein, we employed an integrated bioinformatics approach to determine which immune-related genes (IRGs) modulate the TME and further assess their potential theragnostic (therapeutic + diagnostic) significance in OC progression. Using a robust approach, we developed a predictive risk model to retrospectively examine the clinicopathological parameters of OC patients from The Cancer Genome Atlas (TCGA) database. The validity of the prognostic model was confirmed with data from the International Cancer Genome Consortium (ICGC) cohort. Our approach identified nine IRGs, AKT2, FGF7, FOS, IL27RA, LRP1, OBP2A, PAEP, PDGFRA, and PI3, that form a prognostic model in OC progression, distinguishing patients with significantly better clinical outcomes in the low-risk group. We validated this model as an independent prognostic indicator and demonstrated enhanced prognostic significance when used alongside clinical nomograms for accurate prediction. Elevated LRP1 expression, which indicates poor prognosis in bladder cancer (BLCA), OC, low-grade gliomas (LGG), and glioblastoma (GBM), was also associated with immune infiltration in several other cancers. Significant correlations with immune checkpoint genes (ICGs) highlight the potential importance of LRP1 as a biomarker and therapeutic target. Furthermore, gene set enrichment analysis highlighted LRP1’s involvement in metabolism-related pathways, supporting its prognostic and therapeutic relevance also in BLCA, OC, low-grade gliomas (LGG), GBM, kidney cancer, OC, BLCA, kidney renal clear cell carcinoma (KIRC), stomach adenocarcinoma (STAD), and stomach and oesophageal carcinoma (STES). Our study has generated a novel signature of nine IRGs within the TME across cancers, that could serve as potential prognostic predictors and provide a valuable resource to improve the prognosis of OC.

Abstract Background Though immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear. Methods We investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune‐related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA. Results By comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK–STAT, NF‐κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter‐OS genotypes. Conclusions We used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune‐related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

Abstract Background Triple‐negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. Methods Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single‐cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. Results Five immune‐related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. Conclusion A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients.

Chronic obstructive pulmonary disease (COPD) and lung cancer (LC) are closely related diseases associated with smoking history and dysregulated immune response. However, not all smokers develop the disease, indicating that genetic susceptibility could be important. Therefore, the aim of this study was to search for the potential overlapping genetic biomarkers, with a focus on single nucleotide polymorphisms (SNPs) located in the regulatory regions of immune-related genes. Additionally, the aim was to see if an identified SNP has potentially an effect on proinflamma-tory cytokine concentration in the serum of COPD patients. We extracted summary data of variants in 1511 immune-related genes from COPD and LC genome-wide association studies (GWAS) from the UK Biobank. The LC data had 203 cases, patients diagnosed with LC, and 360 938 controls, while COPD data had 1 897 cases and 359 297 controls. Assuming 1 association/gene, SNPs with a p-value < 3.3 × 10–5 were considered statistically significantly associated with the disease. We identified seven SNPs located in different genes (BAG6, BTNL2, TNF, HCP5, MICB, NCR3, ABCF1, TCF7L1) to be associated with the COPD risk and two with the LC risk (HLA-C, HLA-B), with statistical significance. We also identified two SNPs located in the IL2RA gene associated with LC (rs2386841; p = 1.86 × 10−4) and COPD (rs11256442; p = 9.79 × 10−3) but with lower significance. Functional studies conducted on COPD patients showed that RNA expression of IL2RA, IFNγ and related proinflammatory cytokines in blood serum did not correlate with a specific genotype. Although results presented in this study do not fully support our hypothesis, it is worth to mention that the identified genes/SNPs that were associated with either COPD or LC risk, all were involved in the activation of the NF-κB transcription factor which is closely related to the regulation of the inflammatory response, a condition associated with both pathologies.

Background: Tongue squamous cell carcinoma (TSCC) represents one of the major subsets of head and neck cancer, which is characterized by unfavorable prognosis, frequent lymph node metastasis, and high mortality rate. The molecular events regulating tongue tumorigenesis remain elusive. In this study, we aimed to identify and evaluate immune-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in TSCC. Methods: The lncRNA expression data for TSCC were obtained from The Cancer Genome Atlas (TCGA) and the immune-related genes were downloaded from the Immunology Database and Analysis Portal (ImmPort). Pearson correlation analysis was performed to identify immune-related lncRNAs. The TCGA TSCC patient cohort was randomly divided into training and testing cohorts. In the training cohort, univariate and multivariate Cox regression analyses were used to determining key immune-related lncRNAs, which were then validated through Cox regression analysis, principal component analysis (PCA), and receiver operating characteristic (ROC) analysis in the testing cohort. Results: Six immune-related signature lncRNAs (MIR4713HG, AC104088.1, LINC00534, NAALADL2-AS2, AC083967.1, FNDC1-IT1) were found to have prognostic value in TSCC. Multivariate and univariate cox regression analyses showed that the risk score based on our six-lncRNA model, when compared to other clinicopathological factors (age, gender, stage, N, T), was an important indicator of survival rate. In addition, Kaplan–Meier survival analysis demonstrated significantly higher overall survival in the low-risk patient group than the high-risk patient group within both training and testing cohorts. The ROC analysis indicated that the AUCs for 5-year overall survival were 0.790, 0.691, and 0.721, respectively, for training, testing, and entire cohorts. Finally, PCA analysis demonstrated that the high-risk and low-risk patient groups presented significant deviation regarding their immune status. Conclusions: A prognostic model based on six immune-related signature lncRNAs was established. This six-lncRNA prognostic model has clinical significance and may be helpful in the development of personalized immunotherapy strategies.

Objective: The immune microenvironment influenced clinical outcomes and treatment response of gastric cancer (GC) patients. Though thousands of immune-related genes (IRGs) have been identified, their effects on GC are not fully understood. The objective of the study is to analyze the correlations between the expression and effect of IRGs and clinical outcomes. Moreover, we evaluate the efficacy and value of utilizing the immune-related genes signature as a prognosis prediction model for GC patients. Methods: We identified the differentially expressed IRGs and systematically analyzed their functions. We constructed a novel GC prognostic signature and a new nomogram, Moreover, we explored the infiltrated immune cell types in the immune microenvironment and discussed the genetic variation in GC IRGs. Results: Eight IRGs, including CCL15, MSR1, GNAI1, NR3C1, ITGAV, NMB, AEN, and TGFBR1 were identified. Based on the prognostic signature, GC patients were distinguished into two subtype groups. As verified in multiple datasets, the prognostic signature exhibited good performance in predicting the prognosis (AUC = 0.803, P-value