Abstract

Abnormal autophagy is closely related to the development of cancer. Many studies have demonstrated that autophagy plays an important role in biological function in clear cell renal cell carcinoma (ccRCC). This study aimed to construct a prognostic signature for ccRCC based on autophagy-related genes (ARGs) to predict the prognosis of ccRCC. Differentially expressed ARGs were obtained from ccRCC RNA-seq data in The Cancer Genome Atlas (TCGA) database. ARGs were enriched by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The prognostic ARGs used to construct the risk score models for overall survival (OS) and disease-free survival (DFS) were identified by Cox regression analyses. According to the median value of the risk score, patients were divided into a high-risk group and a low-risk group. The OS and DFS were analyzed by the Kaplan-Meier method. The predictive accuracy was determined by a receiver operating characteristic (ROC) curve analysis. Additionally, we performed stratification analyses based on different clinical variables and evaluated the correlation between the risk score and the clinical variables. The differentially expressed ARGs were mainly enriched in the platinum drug resistance pathway. The prognostic signatures based on 11 ARGs for OS and 5 ARGs for DFS were constructed and showed that the survive time was significantly shorter in the high-risk group than in the low-risk group (P < 0.001). The ROC curve for OS exhibited good predictive accuracy, with an area under the curve value of 0.738. In the stratification analyses, the OS time of the high-risk group was shorter than that of the low-risk group stratified by different clinical variables. In conclusion, an autophagy-related signature for OS we constructed can independently predict the prognosis of ccRCC patient, and provide a deep understanding of the potential biological mechanisms of autophagy in ccRCC.

Highlights

  • Renal cell carcinoma (RCC) is a malignant tumor originating from the renal tubular epithelium

  • As the risk score increased, an increasing number of patients died (Figure 5D). These results showed that the risk score accurately reflect the survival of patients and that the autophagyrelated signature for overall survival (OS) accurately predicts the prognosis of patients

  • These results showed that the prognostic signature for disease-free survival (DFS) can predict the prognosis of clear cell renal cell carcinoma (ccRCC) patients well

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Summary

Introduction

Renal cell carcinoma (RCC) is a malignant tumor originating from the renal tubular epithelium. It is a common malignant tumor of the urinary system, and clear cell renal cell carcinoma (ccRCC) is the most common subtype [1]. Surgical resection is the main treatment for ccRCC, but ccRCC has a poor prognosis and is likely to recur [2]. Common clinical variables, such as the TNM. Because of tumor heterogeneity the TNM stage cannot accurately predict the prognosis of patients [4]. The discovery of new molecular targets in ccRCC is the first requirement for achieving early diagnosis and improving the survival rate of ccRCC patients

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