The effect of a novel glycolysis-related gene signature on progression, prognosis and immune microenvironment of renal c
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RESEARCH ARTICLE
Open Access
The effect of a novel glycolysis-related gene signature on progression, prognosis and immune microenvironment of renal cell carcinoma Fangshi Xu1, Yibing Guan1, Li Xue2, Shanlong Huang2, Ke Gao1, Zhen Yang3 and Tie Chong2*
Abstract Background: Glycolysis is a central metabolic pathway for tumor cells. However, the potential roles of glycolysisrelated genes in renal cell carcinoma (RCC) have not been investigated. Methods: Seven 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. Results: Four 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. Conclusions: The glycolysis-related risk signature is closely associated with RCC prognosis, progression and immune microenvironment. CD44, PLOD1 and PLOD2 may serve as RCC oncogenes. Keywords: Renal cell carcinoma, Glycolysis, Risk signature, Prognosis, Immune microenvironment, GSEA, TCGA, TIMER
* Correspondence: [email protected] 2 Department of Urology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, West Five Road, Xi’an 710000, Shaanxi, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or ex
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