Abstract
BackgroundThe role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration.MethodsClinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature.ResultsFinally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature.ConclusionsA novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.
Highlights
The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysisrelated genes (GRGs) have been proven to be associated with tumor metastasis
A total of 611 patients were extracted from the The Cancer Genome Atlas (TCGA) database, containing 539 renal cancer samples and 72 normal specimens with a mixture of different histologic types of clear cell renal cell carcinoma (ccRCC) included in this study
Functional annotation and pathway enrichment Results of Gene ontology (GO) and Kyoto encyclopedia of genes and genome (KEGG) analyses presented that differently expressed GRGs were remarkably enriched in the biological processes (BP) analysis associated with carbohydrate catabolic process, pyruvate metabolic process, glycolytic process, hexose metabolic process, ATP generation from ADP, pyridine nucleotide metabolic process, glucose metabolic process, pyridine−containing compound metabolic process, nicotinamide nucleotide metabolic process pyruvate biosynthetic process
Summary
The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysisrelated genes (GRGs) have been proven to be associated with tumor metastasis. We aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Renal cell carcinoma (RCC) incidence is second only to bladder cancer and there will be 73,750 newly estimated cases and 14,830 estimated death in the United States, 2020 [1]. Therein, clear cell RCC (ccRCC) accounts for approximately 70–80% of the pathological subtype of RCC. Survival rates of metastatic kidney cancer are still low. Its two-year survival is lower than 20%, and about one-third of patients are found to have tumor metastasis when diagnosed [2, 3].
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