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BackgroundLung is the largest mucosal area of the human body and directly connected to the external environment, facing microbial exposure and environmental stimuli. Therefore, studying the internal microorganisms of the lung is crucial for a deeper understanding of the relationship between microorganisms and the occurrence and progression of lung cancer.MethodsTumor and adjacent nontumor tissues were collected from 38 lung adenocarcinoma patients and used nanopore sequencing technology to sequence the 16s full-length sequence of bacteria, and combining bioinformatics methods to identify and quantitatively analyze microorganisms in tissues, as well as to enrich the metabolic pathways of microorganisms.Resultsthe microbial composition in lung adenocarcinoma tissues is highly similar to that in adjacent tissues, but the alpha diversity is significantly lower than that in adjacent tissues. The difference analysis results show that the bacterial communities of Streptococcaceae, Lactobacillaceae, and Neisseriales were significantly enriched in cancer tissues. The results of metabolic pathway analysis indicate that pathways related to cellular communication, transcription, and protein synthesis were significantly enriched in cancer tissue. In addition, clinical staging analysis of nicotine exposure and lung cancer found that Haemophilus, paralinfluenzae, Streptococcus gordonii were significantly enriched in the nicotine exposure group, while the microbiota of Cardiobactereae and Cardiobacterales were significantly enriched in stage II tumors. The microbiota significantly enriched in IA-II stages were Neisseriaeae, Enterobacteriales, and Cardiobacterales, respectively.ConclusionNanopore sequencing technology was performed on the full length 16s sequence, which preliminarily depicted the microbial changes and enrichment of microbial metabolic pathways in tumor and adjacent nontumor tissues. The relationship between nicotine exposure, tumor progression, and microorganisms was explored, providing a theoretical basis for the treatment of lung cancer through microbial targets.

Purpose: To evaluate the value of quantitative parameters derived from diffusion kurtosis imaging (DKI) and intravoxel incoherent motion (IVIM) in differentiating histologic grades and clinical stages of clear cell renal cell carcinoma (ccRCC). Materials and methods: A total of 65 patients who were surgically and pathologically diagnosed as ccRCC were recruited in this study. In addition to routine renal magnetic resonance imaging examination, all patients underwent preoperative IVIM and DKI. The corresponding diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), mean diffusivity (MD), kurtosis anisotropy (KA), and mean kurtosis (MK) values were obtained. Independentsamples t-test or Mann-Whitney U test was used for comparing the differences in IVIM and DKI parameters among different histologic grades and clinical stages. The diagnostic efficacy of IVIM and DKI parameters was evaluated using the receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used to separately analyze the correlation of each parameter with histologic grades and stages of ccRCC. Results: The D and MD values were significantly higher in low-grade ccRCC than high-grade ccRCC (all p < 0.001) and in low-stage than high-stage ccRCC (all p < 0.05), and the f value of high-stage ccRCC was lower than that of low-stage ccRCC (p = 0.007). The KA and MK values were significantly higher in low-grade than high-grade ccRCC (p = 0.000 and 0.000, respectively) and in low-stage than high-stage ccRCC (p = 0.000 and 0.000, respectively). The area under the curve (AUC) values of D, D*, f, MD, KA, MK, DKI, and IVIM+DKI values were 0.825, 0.598, 0.626, 0.792, 0.750, 0.754, 0.803, and 0.857, respectively, in grading ccRCC and 0.837, 0.719, 0.710, 0.787, 0.796, 0.784, 0.864, 0.823, and 0.916, respectively, in staging ccRCC. The AUC of IVIM was 0.913 in staging ccRCC. The D, D*, and MD values were negatively correlated with the histologic grades and clinical stages (all p < 0.05), and the KA and MK values showed a positive correlation with histologic grades and clinical stages (all p < 0.05). The f value was also negatively correlated with the ccRCC clinical stage (p = 0.008). Conclusion: Both the IVIM and DKI values can be used preoperatively to predict the degree of histologic grades and stages in ccRCC, and the D and MD values have better diagnostic performance in the grading and staging. Also, further slightly enhanced diagnostic efficacy was observed in the model with combined IVIM and DKI parameters. [ABSTRACT FROM AUTHOR]

Condensed abstract: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). This is the first head-tohead propensity score-matched, nationwide population-based cohort study evaluating this survival effect. The results revealed that pretreatment 18FDGPET- CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving radiotherapy or concurrent chemoradiotherapy, especially in the IG-IMRT era. Purpose: No large-scale, well-designed randomized study with a long-term follow-up has evaluated the survival effect of pretreatment 18-fluorodeoxyglucose positron emission tomography-computed tomography (18FDG-PET-CT) on patients with stage IB-IVA cervical cancer receiving imageguided intensity-modulated radiation therapy (IG-IMRT). Therefore, in this propensity score-matched, population-based cohort study, we investigated these survival effects. Patients and methods: We included 4167 patients with stage IB-IVA cervical cancer receiving radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) through the IG-IMRT technique. The patients were categorized into two 1:2 propensity score-matched groups depending on whether they underwent pretreatment 18FDG-PET-CT, and their outcomes were compared. Results: We included 2778 and 1389 patients with cervical cancer in the nonpretreatment and pretreatment PET-CT groups, respectively. Univariable and multivariable analyses revealed an association between pretreatment PET-CT and improved survival in the patients (in the adjusted model, the adjusted hazard ratio [aHR] was 0.88; 95% confidence interval [CI], 0.80-0.97: P = 0.010). Regardless of the cancer stage (early or advanced), pretreatment PET-CT was significantly superior to nonpretreatment PET-CT in terms of all-cause death (aHR, 0.78; 95% CI, 0.60-0.92; P = 0.013 and aHR, 0.90; 95% CI, 0.81-0.99; P = 0.039 for the early [IB-IIA] and advanced stages [IIB-IVA], respectively). Conclusions: Pretreatment 18FDG-PET-CT might be associated with longer survival in patients with stage IB-IVA cervical cancer receiving RT or CCRT, especially in the era of IG-IMRT. [ABSTRACT FROM AUTHOR]

Colon adenocarcinoma (COAD) is one of the deadliest cancers in the world and survival rates vary significantly between early and advanced stage patients. Therefore, the identification of the pathogenesis in the development of COAD and prognostic markers is urgently demanded. Herein, we collected RNA-seq and somatic mutation data of COAD for statistical analysis. Clinical stage-specific differentially expressed genes (DEGs) and tumor development-dependent DEGs were identified. By characterizing the metabolic and immune features of COAD between stages, we found that the energy supply and inflammatory response of advanced tumors were suppressed. Next, the ETS1, AR, GATA1, GATA2, SREBF1, FOXP3, STAT4, and NFKB1 were identified to drive the metabolic and immune-related pathways in the development of COAD. The three potential prognostic markers (HOXC8, IRF7, and CXCL13) were identified based on Cox regression analysis. Additionally, immune infiltration analysis revealed that the resting CD4+ T cell was significantly related to the overall survival (OS) of COAD patients. Collectively, the specific metabolic and immune characteristics of advanced patients and the identified prognostic biomarkers will contribute to the development of precision medicine.

ObjectiveWe performed a pan-cancer analysis to explore the potential mechanisms of FAT4 in 33 different tumors.MethodsIn this study, we selected 33 types of cancers based on the datasets of TCGA (the cancer genome atlas). We analyzed the expression of FAT4 in tumor and normal tissues. Meanwhile, we analyzed the expression levels of FAT4 in tissues from tumors of different stages. Kaplan-Meier survival analysis, Tumor Mutational Burden (TMB), Microsatellite Instability (MSI), immune infiltration analysis, Gene set enrichment analysis (GSEA), and FAT4-related gene enrichment analysis were performed.ResultsFAT4 expression in most tumor tissues was lower than in corresponding control tissues. FAT4 expression was different in different stages of bladder cancer (BLCA), kidney clear cell carcinoma (KIRC), and breast cancer (BRCA). In addition, the expression level of FAT4 in different types of tumors has an important impact on the prognosis of patients. FAT4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. We observed a statistically positive correlation between cancer-associated fibroblasts and FAT4 expression in most tumors. GSEA of BLCA indicated that low FAT4 expression groups were mainly enriched in calcium signaling pathway and chemokine signaling pathway. GSEA analysis of KIRC suggested low FAT4 expression groups were mainly involved in olfactory transduction and oxidative phosphorylation. Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the role of FAT4 in the pathogenesis of cancer may be related to human papillomavirus infection, Hippo signaling pathway, PI3K–Akt signaling pathway, etc. Gene Ontology (GO) enrichment analysis further showed that most of these genes were related to the pathways or cell biology, such as peptidyl–tyrosine phosphorylation, cell junction assembly, protein tyrosine kinase activity, etc.ConclusionOur study summarized and analyzed the antitumor effect of FAT4 in different tumors comprehensively, which aided in understanding the role of FAT4 in tumorigenesis from the perspective of clinical tumor samples. Pan-cancer analysis showed that FAT4 to be novel biomarkers for various cancers prognosis.

PurposeThis study is based on the Surveillance, Epidemiology, and End Results (SEER) program to explore the prognostic differences between signet-ring cell carcinoma (SRC) and intestinal-type gastric carcinoma (ITGC). This study is also based on gene sequencing data from The Cancer Genome Atlas (TCGA) to identify unique genetic contributions to the prognostic differences between the two subtypes of gastric cancer.Patients and MethodsThe clinical data were based on the SEER database from 2004 to 2015. Kaplan–Meier (KM) curves were used to compare 5-year overall survival (OS), and Cox regression was used for univariate and multivariate analyses. Gene expression profiles were obtained from TCGA database, and differentially expressed genes (DEGs) were screened. Functional enrichment analysis, protein interaction and survival analysis will be further carried out. Genes of interest were verified by the Human Protein Atlas, immunohistochemistry, and encyclopedia of Cancer Cell Lines (CCLE). The relationship between genes of interest and immune cell infiltration was also analyzed by Tumor Immune Estimation Resource (TIMER).ResultsCompared with ITGC patients, SRC patients were more likely to be female, tended to be younger, and have a greater tumor distribution in the middle and lower stomach (p < 0.01). SRCs showed a significantly better prognosis than ITGCs (p < 0.01) in early gastric cancer (EGC), while the prognosis of SRCs was significantly worse than ITGCs (p < 0.05) in advanced gastric cancer (AGC). A total of 256 DEGs were screened in SRCs compared to ITGCs, and the enrichment analysis and protein interactions revealed that differential genes were mainly related to extracellular matrix organization. Thrombospondin1 (THBS1) and serpin peptidase inhibitor, clade E, member 1 (SERPINE1) are significantly differentially expressed between SRC and ITGC, which has been preliminarily verified by immunohistochemistry and open-source databases. THBS1 and SERPINE1 are also associated with multiple immune cell infiltrates in gastric cancer.ConclusionsThere were significant differences in the clinicopathological features and prognosis between SRC and ITGC. These results suggest that SRC and ITGC may be two distinct types of tumors with different pathogeneses. We found many codifferentially expressed genes and important pathways between SRC and ITGC. THBS1 and SERPINE1 were significantly differentially expressed in the two types of gastric cancer, and may have potentially important functions.

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1 – 3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1 – 2 and BIRC5 – 6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC. [ABSTRACT FROM AUTHOR]

Inhibitors of apoptosis proteins (IAPs) have been associated with tumor development and progression by affecting apoptosis through cell death signaling pathways. To date, eight IAPs (BIRC1–8) have been identified in mammalian cells. However, the role of IAPs in non–small cell lung cancer (NSCLC) development and progression has not been explored in depth. In this study, we used public datasets and bioinformatics tools to compare the expression, prognostic significance, and function of IAPs in NSCLC and its subtypes. Expression of IAPs in cancer and normal tissues and at different stages of NSCLC was compared with gene expression profiling interactive analysis, and their prognostic significance was analyzed with the Kaplan–Meier Plotter database. The correlations among IAPs were analyzed with the STRING database and SPSS19.0. Functional annotation of IAPs was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment on the basis of the DAVID tool. Among patients with lung adenocarcinoma (LUAD), the expression level of BIRC5 was higher than that in normal samples, and the expression of BIRC1 and BIRC5 significantly varied in different stages. Moreover, the BIRC1–3 and BIRC5 mRNA levels were associated with overall survival (OS), and the BIRC1–2 and BIRC5–6 mRNA levels were associated with progression-free survival (PFS). Among patients with lung squamous cell carcinoma (LUSC), the expression level of BIRC1 was lower and that of BIRC5 was higher than those in normal tissues, and BIRC5 expression significantly varied in different stages. BIRC1 expression was associated with OS, whereas BIRC2 and BIRC6 expression was associated with PFS. Enrichment analysis showed that most IAPs are associated with ubiquitin- and apoptosis-related pathways. Collectively, this study suggests BIRC5 as a potential diagnostic and staging marker, BIRC1 as a potential marker of OS, and BIRC2 and BIRC6 as potential PFS markers for patients with NSCLC. These highlight new targets for the early detection, treatment, and management of NSCLC.