Abstract

Hypoxia is a significant clinical feature and regulates various tumor processes in clear cell renal carcinoma (ccRCC). Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with the survival outcomes of ccRCC patients and regulates hypoxia-induced tumor processes. Thus, this study aimed to develop a hypoxia-related lncRNA (HRL) prognostic model for predicting the survival outcomes in ccRCC. LncRNAs in ccRCC samples were extracted from The Cancer Genome Atlas database. Hypoxia-related genes were downloaded from the Molecular Signatures Database. A co-expression analysis between differentially expressed lncRNAs and hypoxia-related genes in ccRCC samples was performed to identify HRLs. Univariate and multivariate Cox regression analyses were performed to select nine optimal lncRNAs for developing the HRL model. The prognostic model showed good performance in predicting prognosis among patients with ccRCC, and the validation sets reached consistent results. The model was also found to be related to the clinicopathologic parameters of tumor grade and tumor stage and to tumor immune infiltration. In conclusion, our findings indicate that the hypoxia-lncRNA assessment model may be useful for prognostication in ccRCC cases. Furthermore, the nine HRLs included in the model might be useful targets for investigating the tumorigenesis of ccRCC and designing individualized treatment strategies.

Highlights

  • Renal cell carcinoma (RCC) causes more than 100,000 deaths per year [1]

  • Of the 137 hypoxia genes obtained from the Molecular Signatures Database V7.2, four genes (FGF3, LIN28B, MMP13, and TH) were excluded owing to a lack of over 50% expression information

  • 598 hypoxia-related lncRNA (HRL) were confirmed by co-expression analyses between hypoxia genes and differentially expressed long non-coding RNAs (lncRNAs) (P ≤ 0.001, Spearman correlation coefficient ≥0.4)

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Summary

Introduction

Renal cell carcinoma (RCC) causes more than 100,000 deaths per year [1]. Target therapy and immunotherapy have improved the prognosis of RCC patients [2], the 5-year survival rate remains less than 10%. Clear cell renal cell carcinoma (ccRCC) is the main subtype of RCC, accounting for 70–75% of all RCC cases [3]. The prognosis and treatment of lncRNA Prognostic Model for ccRCC ccRCC are primarily based on the tumor stage. The outcomes still vary among patients with the same tumor stage because of molecular heterogeneity [4]. It is vital to identify individualized biomarkers that can identify patients at high risk of death and help stratify patients for individual treatment to optimize the therapeutic effect

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