Abstract
We examined the role of differentially expressed autophagy-related genes (DEARGs) in clear cell Renal Cell Carcinoma (ccRCC) using high-throughput RNA-seq data from The Cancer Genome Atlas (TCGA). Cox regression analyses showed that 5 DEARGs (PRKCQ, BID, BAG1, BIRC5, and ATG16L2) correlated with overall survival (OS) and 4 DEARGs (EIF4EBP1, BAG1, ATG9B, and BIRC5) correlated with disease-free survival (DFS) in ccRCC patients. Multivariate Cox regression analysis using the OS and DFS prognostic risk models showed that expression of the nine DEARGs accurately and independently predicted the risk of disease recurrence or progression in ccRCC patients (area under curve or AUC values > 0.70; all p < 0.05). Moreover, the DEARGs accurately distinguished healthy individuals from ccRCC patients based on receiver operated characteristic (ROC) analyses (area under curve or AUC values > 0.60), suggesting their potential as diagnostic biomarkers for ccRCC. The expression of DEARGs also correlated with the drug sensitivity of ccRCC cell lines. The ccRCC cell lines were significantly sensitive to Sepantronium bromide, a drug that targets BIRC5. This makes BIRC5 a potential therapeutic target for ccRCC. Our study thus demonstrates that DEARGs are potential diagnostic and prognostic biomarkers and therapeutic targets in ccRCC.
Highlights
Clear cell renal cell carcinoma accounts for 70–80% of cases of renal cell carcinoma (RCC), which is one of the most common malignant tumors of the urinary system [1, 2]
We explored the prognostic significance of autophagy-related genes (ARGs) in Clear cell renal cell carcinoma (ccRCC) tumors using information derived from highthroughput expression profiles in public databases
The data showed that expression of 19 differentially expressed autophagy-related genes (DEARGs) each significantly correlated with the overall survival (OS) (p < 0.05) and the disease-free survival (DFS) (p < 0.05) of ccRCC patients (Supplementary Figure 1)
Summary
Clear cell renal cell carcinoma (ccRCC) accounts for 70–80% of cases of renal cell carcinoma (RCC), which is one of the most common malignant tumors of the urinary system [1, 2]. Autophagy is an important biological process that maintains cellular homeostasis by degrading aged or damaged proteins and organelles within the lysosomes [4, 5]. Higher levels of autophagy in cardiomyocytes are associated with heart failure [8, 9]. In ischemic heart disease, induction of autophagy is required to maintain energy homeostasis and survival of cardiomyocytes [10]. In www.aging-us.com early stages of many cancers, autophagy suppresses the transformation and growth of cancer cells. In later stages of tumors, autophagy promotes rapid growth of malignant cells by degrading and recycling components of damaged or aged organelles to meet their metabolic demands for rapid growth [11]. The levels of autophagy proteins can regulate tumor growth and progression [12]
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