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The kidney renal papillary cell carcinoma (KIRP) is a relatively rare type of renal cell carcinoma (RCC). Currently, most kidney cancer studies primarily focus on RCC, and there has been no investigation to find a robust signature to predict the survival outcome of KIRP patients. In this study, we constructed a competing endogenous RNA (ceRNA) network, including 1,251 lncRNA–miRNA–mRNA interactions. Eight differentially expressed genes (IGF2BP3, PLK1, LINC00200, NCAPG, CENPF, miR-217, GAS6-As1, and LRRC4) based on the TCGA database were selected. The prognostic signature was established by combining the univariate Cox regression method and a stepwise regression method, with its predictive value validated by time-dependent receiver operating characteristic (ROC) curves. In conclusion, we identified eight prognostic signatures with using ceRNA networks. Our study provided a global view and a systematic dissection on KIRP prognosis biomarkers, and the eight identified genes might be used as new and important prognostic factors involved in KIRP pathogenesis.

There are several studies on the deregulated gene expression profiles in kidney cancer, with varying results depending on the tumor histology and other parameters. None of these, however, have identified the networks that the co-deregulated genes (co-DEGs), across different studies, create. Here, we reanalyzed 10 Gene Expression Omnibus (GEO) studies to detect and annotate co-deregulated signatures across different subtypes of kidney cancer or in single-gene perturbation experiments in kidney cancer cells and/or tissue. Using a systems biology approach, we aimed to decipher the networks they form along with their upstream regulators. Differential expression and upstream regulators, including transcription factors [MYC proto-oncogene (MYC), CCAAT enhancer binding protein delta (CEBPD), RELA proto-oncogene, NF-kB subunit (RELA), zinc finger MIZ-type containing 1 (ZMIZ1), negative elongation factor complex member E (NELFE) and Kruppel-like factor 4 (KLF4)] and protein kinases [Casein kinase 2 alpha 1 (CSNK2A1), mitogen-activated protein kinases 1 (MAPK1) and 14 (MAPK14), Sirtuin 1 (SIRT1), Cyclin dependent kinases 1 (CDK1) and 4 (CDK4), Homeodomain interacting protein kinase 2 (HIPK2) and Extracellular signal-regulated kinases 1 and 2 (ERK1/2)], were computed using the Characteristic Direction, as well as GEO2Enrichr and X2K, respectively, and further subjected to GO and KEGG pathways enrichment analyses. Furthermore, using CMap, DrugMatrix and the LINCS L1000 chemical perturbation databases, we highlight putative repurposing drugs, including Etoposide, Haloperidol, BW-B70C, Triamterene, Chlorphenesin, BRD-K79459005 and β-Estradiol 3-benzoate, among others, that may reverse the expression of the identified co-DEGs in kidney cancers. Of these, the cytotoxic effects of Etoposide, Catecholamine, Cyclosporin A, BW-B70C and Lasalocid sodium were validated in vitro. Overall, we identified critical co-DEGs across different subtypes in kidney cancer, and our results provide an innovative framework for their potential use in the future.

Background: Defects in methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) expression have earlier been examined in only a few human cancers. Objectives: Multi-omics profiling of MTHFD1L as a shared biomarker in distinct subtypes of human cancers. Methods: In the current study, for the multi-omics analysis of MTHFD1L in 24 major subtypes of human cancers, a comprehensive in silico approach was adopted to mine different open access online databases including UALCAN, Kaplan-Meier (KM) plotter, LOGpc, GEPIA, Human Protein Atlas (HPA), Gene Expression across Normal and Tumor tissue (GENT2), MEXPRESS, cBioportal, STRING, DAVID, TIMER, and Comparative Toxicogenomics Database (CTD). Results: We noticed that the expression of MTHFD1L was significantly higher in all the analyzed 24 subtypes of human cancers as compared with the normal controls. Moreover, MTHDF1L overexpression was also found to be significantly associated with the reduced overall survival (OS) duration of Bladder urothelial cancer (BLCA), Head and neck cancer (HNSC), Kidney renal papillary cell carcinoma (KIRP), Lung adenocarcinoma (LUAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that MTHFD1L plays a significant role in the development and progression of these cancers. We further noticed that MTHFD1L was also overexpressed in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of MTHFD1L-associated genes in five diverse pathways. We also explored few interesting correlations between MTHFD1L expression and its promoter methylation, genetic alterations, CNVs, and between CD8+ T immune cells level. Conclusion: In conclusion, our results elucidated that MTHFD1L can serve as a shared diagnostic and prognostic biomarker in BLCA, HNSC, KIRP, LUAD, and UCEC patients of different clinicopathological features. [ABSTRACT FROM AUTHOR]

5-methylcytosine (m5C) is a post-transcriptional RNA modification identified, m5C readers can specifically identify and bind to m5C. ALYREF and YBX1 as members of m5C readers that have garnered increasing attention in cancer research. However, comprehensive analysis of their molecular functions across pancancer are lacking. Using the TCGA and GTEx databases, we investigated the expression levels and prognostic values of ALYREF and YBX1. Additionally, we assessed the tumor microenvironment, immune checkpoint-related genes, immunomodulators, Tumor Immune Dysfunction and Exclusion (TIDE) score and drug resistance of ALYREF and YBX1. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses were performed to investigate the potential functions associated with m5C readers and coexpressed genes. Aberrant expression of ALYREF and YBX1 was observed and positively associated with prognosis in KIRP, LGG and LIHC. Furthermore, the expression levels of ALYREF and YBX1 were significantly correlated with immune infiltration of the tumor microenvironment and immune-related modulators. Last, our analysis revealed significant correlations between ALYREF, YBX1 and eIFs. Our study provides a substantial understanding of m5C readers and the intricate relationship between ALYREF, YBX1, eIFs, and mRNA dynamics. Through multidimensional analysis of immune infiltration and drug sensitivity/resistance in ALYREF and YBX1, we propose a possibility for combined modality therapy utilizing m5C readers. [ABSTRACT FROM AUTHOR]

Background: GPRIN1 may be a novel tumor regulator, but its role and mechanism in tumors are still unclear. Methods: First, a pan‐cancer correlation analysis was conducted on the expression and prognosis of GPRIN1 based on the data downloaded from The Cancer Genome Atlas (TCGA) database. Second, the Starbase database was used to predict the upstream miRNAs and lncRNAs of GPRIN1, and the expression analysis, survival analysis, and correlation analysis were performed to screen the microRNA (miRNAs)/long non‐coding RNAs (lncRNAs) that had a correlation with kidney renal papillary cell carcinoma (KIRP) or lung adenocarcinoma (LUAD). Third, the CIBERSORT algorithm was employed to calculate the proportion of various types of immune cells, and then the R packages were used for evaluating the relation between GPRIN1 expression and tumor immune cell infiltration as well as between GPRIN1 and the immune cell biomarker. Finally, the correlation analysis was made on GPRIN1 and immune checkpoints (CD274, CTLA4, and PDCD1). Results: The pan‐cancer analysis suggested that GPRIN1 was up‐expressed in KIRP and LUAD, and it correlated with poor prognosis. LINC00894/MMP25‐AS1/SNHG1/LINC02298/MIR193BHG‐miR‐140‐3p was likely to be the most promising upstream regulation pathway of GPRIN1. Upexpression of LINC00894/MMP25‐AS1/SNHG1/LINC02298/MIR193BHG and downexpression of miR‐140‐3p were found relevant with poor outcomes of KIRP and LUAD. GPRIN1 expression was significantly correlated with tumor immune cell infiltration, immune cell biomarkers, and immune checkpoints. Conclusions: The competitive endogenous (ceRNA) of miR‐140‐3p‐GPRIN1 axis and its upstream lncRNAs are closely related to KIRP and LUAD, and might affect the prognosis and therapeutic effect of KIRP and LUAD. [ABSTRACT FROM AUTHOR]

Simple Summary: Renal cell carcinoma (RCC) is one of the most life-threatening urological neoplasms. The tumor microenvironment comprising immune cell infiltration is a key factor for treatment response and survival of RCC patients. In addition, several studies focused on the involvement of the microbiome in tumor progression via the secretion of metabolic by-products such as succinate. In this study, we have highlighted the potential role of the succinate receptor, SUCNR1, in modulating the tumor microenvironment in the RCC subtypes. Our data displayed a distinct association of SUCNR1 with the microbiome signature, tumor immune infiltrates, and immunomodulators in two different RCC subtypes. This correlation could have potentially contributed to the different survival outcomes of the RCC patients. Thus, SUCNR1 may serve as a promising prognostic factor that might help in improving therapeutic interventions. The succinate receptor, SUCNR1, has been attributed to tumor progression, metastasis, and immune response modulation upon its activation via the oncometabolite succinate. Nonetheless, little is known about the prognostic relevance of SUCNR1 and its association with tumor immune infiltrates and microbiota in renal cell carcinoma (RCC). Herein, publicly available platforms including Human Protein Atlas, cBioPortal, TIMER2.0, and TISIDB were utilized to depict a divergent implication of SUCNR1 in the immune microenvironment of clear cell RCC (KIRC) and papillary RCC (KIRP); the two major subtypes of RCC. Our results showed that the SUCNR1 expression level was augmented in RCC compared to other solid cancers, yet with opposite survival rate predictions in RCC subtypes. Consequently, a higher expression level of SUCNR1 was associated with a good disease-specific survival rate (p = 5.797 × 10−5) in KIRC patients albeit a poor prognostic prediction in KIRP patients (p = 1.9282 × 10−3). Intriguingly, SUCNR1 was mainly correlated to immunomodulators and diverse immune infiltrates in KIRP. Additionally, the SUCNR1 was mostly associated with a repertoire of microbes including beneficial bacteria that likely influenced a better disease-specific survival rate in KIRC. Our findings illustrate a significant novel subtype-specific role of SUCNR1 in RCC which potentially modulates tumor immune infiltration and microbiome signature, hence altering the prognosis of cancer patients. [ABSTRACT FROM AUTHOR]

The present study investigates the molecular dynamics of Myc in normal precursors and in different stages (I/II/III/IV) of cohorts of renal cancer using two distinct yet complementary approaches: gene expression and gene coexpression. We also analysed the variation of coexpression networks of Myc through the stage-wise progression of renal cancer cohorts. Myc expression is significantly higher in stage I compared to normal tissue but changed inconsistently across stages of renal cancer. We identified that Myc consistently coexpressed with fourteen genes in the KIPAN [Pan-kidney cohort (KICH + KIRC + KIRP)] and eight in the KIRC (Kidney renal clear cell carcinoma) across all stages, providing potential prognostic and diagnostic biomarkers. Coexpression network complexity decreased from normal precursor tissues to associated tumour stage I in KIPAN and KIRC but was inconsistent after that. In the process of cancer development, there is generally lower cross-tissue cancer network homology observed among coexpressed genes with Myc during the normal to the stage I compared to the stage-wise progression of cancer. Overall, this research provides novel perceptions of the molecular causes of kidney cancer. It also highlights potential genes and pathways crucial for diagnosing and treating this disease. [ABSTRACT FROM AUTHOR]

Lymphocyte activating gene-3 (LAG3) is a distinctive T cell co-receptor that is expressed on the surface of lymphocytes. It plays a special inhibitory immune checkpoint role due to its unique domain and signaling pattern. Our aim is to explore the correlation between LAG3 in cancers and physiological processes related to a range of cancers, as well as build LAG3-related immunity and prognostic models. By comprehensively using of datasets and methods from TCGA, GTE-x and GEO databases, cBioPortal, HPA, Kaplan-Meier Plotter, Spearman, CellMinerTM, we delved deeper into the potential impact of the LAG3 in cancer development. These include expression differences, Localization of tumor cell subsets, immune infiltration, matrix infiltration, gene mutations, DNA methylation, signaling pathways and prognosis. Furthermore, we explored LAG3 interactions with different drugs. LAG3 is highly expressed in ACC (p < 0.001), BRCA (p < 0.001), DLBC (p < 0.001), ESCA (p < 0.001), GBM (p < 0.001), HNSC (p < 0.001), KIRC (p < 0.001), LGG (p < 0.001), LUAD (p < 0.01), LUSC (p < 0.001), PAAD (p < 0.001), PCPG (p < 0.01), SKCM (p < 0.001), STAD (p < 0.001), TGCT (p < 0.001) and THCA (p < 0.05), while lowly expressed in COAD (p < 0.001), LIHC (p < 0.05), OV (p < 0.001), PRAD (p < 0.001), READ (p < 0.001), UCEC (p < 0.001) and UCS (p < 0.001). High expression of LAG3 correlates with longer overall survival (OS) in BLCA (HR = 0.67, p < 0.05), CESC (HR = 0.3, p < 0.001), HNSC (HR = 0.67, p < 0.01), LUSC (HR = 0.71, p < 0.05), OV (HR = 0.65, p < 0.01), STAD (HR = 0.68, p < 0.05), and UCEC (HR = 0.57, p < 0.01). Conversely, in KIRC (HR = 1.85, p < 0.001), KIRP (HR = 2.81, p < 0.001), and THYM (HR = 8.92, p < 0.001), high LAG3 expression corresponds to shorter OS. Comprehensive results for recurrence-free survival (RFS) indicate that LAG3 acts as a protective factor in BLCA, CESC, OV, and UCEC. Moreover, LAG3 is widely expressed in tumor-associated lymphocytes, positively correlating with tumor immune scores and stromal scores, and significantly present in the C2 immune subtype across various tumors. High LAG3 expression correlates with increased immune infiltration. LAG3 shows associations with MSI, TMB, and the MMR system, participating in multiple signaling pathways including the T cell receptor pathway. It also demonstrates positive correlations with sensitivity to eleven different drugs. Unlike traditional inhibitory immune checkpoints, LAG3 exhibits dual roles in clinical and immune prognostication across pan-cancers, making it a significant predictive factor. In some cancers, LAG3 serves as a risk factor, indicating adverse clinical outcomes. Conversely, in BLCA, CESC, OV, and UCEC, LAG3 acts as a protective factor associated with longer patient survival. LAG3 demonstrates strong associations within tumor immunity, participating in a range of immune and inflammatory signaling pathways. Elevated levels of LAG3 are linked not only to T cell exhaustion but also to increased immune infiltration and polarization towards M1 macrophages. [ABSTRACT FROM AUTHOR]

Background: Cluster of differentiation 24 (CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a "don't eat me" signaling molecule in tumor immune. This study aimed to investigate the potential features of CD24 in pan-cancer. Methods: The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package "ESTIMATE" was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman's correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of CD24 in LIHC. Results: CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally, CD24 was overexpressed in most tumors, with high CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally, CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC. Conclusion: CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker. [ABSTRACT FROM AUTHOR]

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pancancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large Bcell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention. [ABSTRACT FROM AUTHOR]

Spindle component 25 (SPC25) is one of the four proteins that make up the nuclear division cycle 80 (NDC80) complex, the other three components being Ndc80p, Nuf2p, and spindle component 24. Deregulation of the components of this complex can lead to uncontrolled proliferation and reduced apoptosis. However, the prognostic and immunotherapeutic value of SPC25 in pan-cancer remains unclear. Data from the UCSC Xena, TIMER2.0, and TCGA were analyzed to investigate the overall differential expression of SPC25 across multiple cancer types. The survival prognosis, clinical features, and genetic changes of SPC25 were also evaluated. Finally, the relationship between SPC25 and immunotherapy response was further explored through Gene Set Enrichment Analysis, tumor microenvironment, and immune cell infiltration. The transcription and protein expression of SPC25 were significantly increased in most cancer types and had prognostic value for the survival of certain cancer patients such as ACC, CESC, KIRC, KIRP, LIHC, LUAD, MESO, STAD, THYM, and UCEC. In some cancer types, SPC25 expression was also markedly correlated with the TMB, MSI, and clinical characteristics. Gene Set Enrichment Analysis showed that SPC25 was significantly associated with immune-related pathways. In addition, it was also confirmed that the expression level of SPC25 was strongly correlated with immune cell infiltration, immune checkpoint genes, immune regulatory genes, Ferroptosis-related genes, Cuproptosis-related genes, and lactate metabolism-related genes. This study comprehensively explored the potential value of SPC25 as a prognostic and immunotherapeutic marker for pan-cancer, providing new direction and evidence for cancer therapy. [ABSTRACT FROM AUTHOR]

Purpose: Establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the mitotic S-phase adhesins acetylation and is responsible for bridging two sister chromatids. However, present ESCO2 cancer research is limited to a few cancers. No systematic pan-cancer analysis has been conducted to investigate its role in diagnosis, prognosis, and effector function. Methods: We thoroughly examined the ESCO2 carcinogenesis in pan-cancer by combining public databases such as The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UALCAN and Tumor Immune Single-cell Hub (TISCH). The analysis includes differential expression analysis, survival analysis, cellular effector function, gene mutation, single cell analysis, and tumor immune cell infiltration. Furthermore, we confirmed ESCO2's impacts on clear cell renal cell carcinoma (ccRCC) cells' proliferative and invasive capacities in vitro. Results: In our study, 30 of 33 cancer types exhibited considerably greater levels of ESCO2 expression in tumor tissue using TCGA and GTEx databases, whereas acute myeloid leukemia (LAML) exhibited significantly lower levels. Kaplan-Meier survival analyses in adrenocortical carcinoma (ACC), kidney chromophobe (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), mesothelioma (MESO), and pancreatic adenocarcinoma (PAAD) demonstrated that tumor patients with high ESCO2 expression have short survival periods. However, in thymoma (THYM), colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), ESCO2 was a favorable prognostic factor. Moreover, ESCO2 expression positively correlates with tumor stage and tumor size in several cancers, including LIHC, KIRC, KIRP and LUAD. Function analysis revealed that ESCO2 participates in mitosis, cell cycle, DNA damage repair, and other processes. CDK1 was identified as a downstream gene regulated by ESCO2. Furthermore, ESCO2 might also be implicated in immune cell infiltration. Finally, ESCO2'S knockdown significantly inhibited the A498 and T24 cells' proliferation, invasion, and migration. Conclusions: In conclusion, ESCO2 is a possible pan-cancer biomarker and oncogene that can reliably predict the prognosis of cancer patients. ESCO2 was also implicated in the cell cycle and proliferation regulation. In a nutshell, ESCO2 is a therapeutically viable and dependable target. [ABSTRACT FROM AUTHOR]

Objective: It has been demonstrated that IDO1, a target of immune checkpoint inhibition, functions as an oncogene in the majority of human malignancies. IDO1's function in human pan-cancers hasn't been thoroughly studied, though. Materials and methods: The Kaplan–Meier (K-M) and COX analyses were applied to the survival analysis. Furthermore, we used Spearman's correlation analysis to examine the associations between IDO1 and microsatellite instability (MSI), DNA methyltransferases (DNMTs), tumor mutational burden (TMB), the associated genes of mismatch repair (MMR), and immune checkpoint biomarkers. Moreover, immunohistochemical analysis and qRT-PCR were used to evaluate IDO1's expression in pan-cancer cells. Results: The findings of this study reveal that IDO1 has abnormal expression in a number of malignancies and is related to the prognosis for UVM, LGG, KIRP, GBM, LAML, OV, READ, MESO, SARC, SKCM, and HNSC. Furthermore, the aberrant IDO1 expression was connected to the TMB, MSI, MMR, drug sensitivity, immune cells infiltrating, and tumor immune microenvironment across a variety of cancer types. The PCR results showed that in contrast to normal cells, IDO1 was found to be significantly highly expressed in breast cancer cells and hepatocellular carcinoma cells, and significantly lowly expressed in gastric cancer cells. Conclusion: The clinical treatment of IDO1 is now better supported by a theoretical basis and guidelines provided by our study. [ABSTRACT FROM AUTHOR]

Neuropilin-1 (NRP1) is a recently identified glycoprotein that is an important host factor for SARS-CoV-2 infection. On the other hand, angiotensin-converting enzyme-2 (ACE2) acts as a receptor for SARS-CoV-2. Additionally, both NRP1 and ACE2 express in the kidney and are associated with various renal diseases, including renal carcinoma. Therefore, the expression profiles of NRP1 and ACE2 in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) patients from the various cancer databases were investigated along with their impact on patients' survivability. In addition, coexpression analysis of genes involved in COVID-19, KIRC, and KIRP concerning NRP1 and ACE2 was performed. The results demonstrated that both t NRP1 and ACE2 expressions are upregulated in KIRC and KIRP compared to healthy conditions and are significantly correlated with the survivability rate of KIRC patients. A total of 128 COVID-19-associated genes are coexpressed, which are positively associated with NRP1 and ACE2 both in KIRC and KIRP. Therefore, it might be suggested that, along with the ACE2, high expression of the newly identified host factor NRP1 in renal carcinomas may play a vital role in the increased risk of SARS-CoV-2 infection and survivability of COVID-19 patients suffering from kidney cancers. The findings of this investigation will be helpful for further molecular studies and prevention and/or treatment strategies for COVID-19 patients associated with renal carcinomas. [ABSTRACT FROM AUTHOR]

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Background: The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) plays critical functions in innate immune responses via the production of the second messenger cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which stimulates the adaptor stimulator of interferon genes (STING). However, the clinical relevance and prognostic value of the cGAS-STING pathway in human cancers remains largely unexplored.Methods: A gene signature related to the cGAS-STING score was identified. The pan-cancer landscape of cGAS-STING expression was calculated using the RNAseq data acquired from the TCGA cohort. Tumor-infiltrating immune cells (TIICs) were determined by the ssGSEA method. Kaplan-Meier curves, Cox regression analyses, and the area under the curve (AUC) were employed to decipher the predictive value of cGAS-STING risk score and TIICs across several human cancers.Results: Most tumor tissues displayed a higher cGAS-STING score compared with their corresponding nontumor tissues, except for prostate adenocarcinoma (PRAD) and uterine corpus endometrial carcinoma (UCEC). Higher cGAS-STING score was closely associated with poor clinical outcome of kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP), whereas the cGAS-STING score predicted a better prognosis in pheochromocytoma and paraganglioma (PCPG). Enrichment analysis showed that cGAS-STING was profoundly implicated in diverse immune-related pathways in KIRC, KIRP, and PCPG. Significant positive correlations were noticed between cGAS-STING score and TIICs, including activated CD8+ T cells, activated CD4+ T cells, monocytes, and mast cells. Finally, the cGAS-STING score was revealed to be an independent prognostic factor for KIRC patients and possessed a strong predictive power for the prognostic evaluation of KIRC and KIRP patients.Conclusions: We constructed a cGAS-STING gene signature to predict survival and tumor immunity across human cancers, which can serve as a novel prognostic indicator and therapeutic target, especially in KIRC and KIRP. [ABSTRACT FROM AUTHOR]