The effect of a novel glycolysis-related gene signature on progression, prognosis and immune microenvironment of renal cell carcinoma

Fangshi Xu,Tie Chong,Yibing Guan,Li Xue,Ke Gao,Shanlong Huang,Zhen Yang

doi:10.1186/s12885-020-07702-7

Fangshi Xu, Tie Chong + Show 5 more

Open Access

https://doi.org/10.1186/s12885-020-07702-7

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Abstract

BackgroundGlycolysis is a central metabolic pathway for tumor cells. However, the potential roles of glycolysis-related genes in renal cell carcinoma (RCC) have not been investigated.MethodsSeven glycolysis-related gene sets were selected from MSigDB and were analyzed through GSEA. Using TCGA database, the glycolysis-related gene signature was constructed. Prognostic analyses were based on the Kaplan–Meier method. The cBioPortal database was employed to perform the mutation analyses. The CIBERSORT algorithm and TIMER database were used to determine the immunological effect of glycolytic gene signature. The expressions in protein level of eight glycolytic risk genes were determined by HPA database. Finally, qPCR, MTT and Transwell invasion assays were conducted to validate the roles of core glycolytic risk genes (CD44, PLOD1 and PLOD2) in RCC.ResultsFour glycolysis-related gene sets were significantly enriched in RCC samples. The glycolytic risk signature was constructed (including CD44, PLOD2, KIF20A, IDUA, PLOD1, HMMR, DEPDC1 and ANKZF1) and identified as an independent RCC prognostic factor (HR = 1.204). Moreover, genetic alterations of glycolytic risk genes were uncommon in RCC (10.5%) and glycolytic risk signature can partially affect immune microenvironment of RCC. Six glycolytic risk genes (except for IDUA and HMMR) were over-expression in A498 and 786-O renal cancer cells through qPCR test. MTT and Transwell assays revealed that silencing of CD44, PLOD1 and PLOD2 suppressed the proliferation and invasion of renal cancer cells.ConclusionsThe glycolysis-related risk signature is closely associated with RCC prognosis, progression and immune microenvironment. CD44, PLOD1 and PLOD2 may serve as RCC oncogenes.

Highlights

Glycolysis is a central metabolic pathway for tumor cells
Glycolytic metabolism is significantly enriched in renal cell carcinoma (RCC) samples Five hundred thirty-seven RCC samples from the Cancer Genome Atlas (TCGA) database were included in our bioinformatic analyses (Table 1)
Four gene sets were significantly enriched in RCC samples, namely Biocarta feeder pathway, Biocarta glycolysis pathway, Reactome glycolysis and Hallmark glycolysis (Table 2)

Summary

Introduction

The potential roles of glycolysisrelated genes in renal cell carcinoma (RCC) have not been investigated. Renal cell carcinoma (RCC) is the third most common genitourinary cancer, accounting for approximatively 2.2% of new cancer cases worldwide [1]. It has a high mortality rate, which results in almost 200,000 deaths/ year, accounting for 1.8% of all cancer-related deaths [2]. Radical nephrectomy is the main treatment for early stage RCC patients, with a 72% 5-year overall survival rate (OSR) [3]. Molecular-targeted drugs improve survival time of metastatic patients, the median survival time is still less than 3 years [6]. It is still urgent and challenging to explore RCC molecular mechanisms and find potential therapeutic targets and prognostic biomarkers

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