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Prognostic value of immune-related genes in clear cell renal cell carcinoma.

ABSTRACT: Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma, and immune-related genes (IRGs) are key contributors to its development. In this study, the gene expression profiles and clinical data of ccRCC patients were downloaded from The Cancer Genome Atlas database and the cBioPortal database, respectively. IRGs were obtained from the ImmPort database. We analyzed the expression of IRGs in ccRCC, and discovered 681 that were differentially expressed between ccRCC and normal kidney tissues. Univariate Cox regression analysis was used to identify prognostic differentially expressed IRGs (PDEIRGs). Using Lasso regression and multivariate Cox regression analyses, we detected seven optimal PDEIRGs (PLAU, ISG15, IRF9, ARG2, RNASE2, SEMA3G and UCN) and used them to construct a risk model to predict the prognosis of ccRCC patients. This model accurately stratified patients with different survival outcomes and precisely identified patients with different mutation burdens. Our findings suggest the seven PDEIRGs identified in this study are valuable prognostic predictors in ccRCC patients. These genes could be used to investigate the developmental mechanisms of ccRCC and to design individualized treatments for ccRCC patients.

SUBMITTER: Wan B

PROVIDER: S-EPMC6932908 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Prognostic value of immune-related genes in clear cell renal cell carcinoma.

Wan Bangbei B Liu Bo B Huang Yuan Y Yu Gang G Lv Cai C

Aging 20191210 23

Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma, and immune-related genes (IRGs) are key contributors to its development. In this study, the gene expression profiles and clinical data of ccRCC patients were downloaded from The Cancer Genome Atlas database and the cBioPortal database, respectively. IRGs were obtained from the ImmPort database. We analyzed the expression of IRGs in ccRCC, and discovered 681 that were differentially expressed ...[more]

PMID: 31821170

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Project description:Numerous studies have shown that the Krüppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.

Dataset Information

Prognostic value of immune-related genes in clear cell renal cell carcinoma.

Publications

Prognostic value of immune-related genes in clear cell renal cell carcinoma.

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