Abstract
BackgroundProstate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide. Autophagy-related genes (ARGs) may play an essential role in multiple biological processes of prostate cancer. However, ARGs expression signature has rarely been used to investigate the association between autophagy and prognosis in PCa. This study aimed to identify and assess prognostic ARGs signature to predict overall survival (OS) and disease-free survival (DFS) in PCa patients.MethodsFirst, a total of 234 autophagy-related genes were obtained from The Human Autophagy Database. Then, differentially expressed ARGs were identified in prostate cancer patients based on The Cancer Genome Atlas (TCGA) database. The univariate and multivariate Cox regression analysis was performed to screen hub prognostic ARGs for overall survival and disease-free survival, and the prognostic model was constructed. Finally, the correlation between the prognostic model and clinicopathological parameters was further analyzed, including age, T status, N status, and Gleason score.ResultsThe OS-related prognostic model was constructed based on the five ARGs (FAM215A, FDD, MYC, RHEB, and ATG16L1) and significantly stratified prostate cancer patients into high- and low-risk groups in terms of OS (HR = 6.391, 95% CI = 1.581– 25.840, P < 0.001). The area under the receiver operating characteristic curve (AUC) of the prediction model was 0.84. The OS-related prediction model values were higher in T3-4 than in T1-2 (P = 0.008), and higher in Gleason score > 7 than ≤ 7 (P = 0.015). In addition, the DFS-related prognostic model was constructed based on the 22 ARGs (ULK2, NLRC4, MAPK1, ATG4D, MAPK3, ATG2A, ATG9B, FOXO1, PTEN, HDAC6, PRKN, HSPB8, P4HB, MAP2K7, MTOR, RHEB, TSC1, BIRC5, RGS19, RAB24, PTK6, and NRG2), with AUC of 0.85 (HR = 7.407, 95% CI = 4.850–11.320, P < 0.001), which were firmly related to T status (P < 0.001), N status (P = 0.001), and Gleason score (P < 0.001).ConclusionsOur ARGs based prediction models are a reliable prognostic and predictive tool for overall survival and disease-free survival in prostate cancer patients.
Highlights
Prostate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide
There are still a large number of PCa patients who develop the resistance to androgen deprivation therapy (ADT) and become castrationresistant PCa (CRPC), which results in a short survival time [8]
Expressed Autophagyrelated genes (ARGs) between prostate cancer and adjacent non‐tumor tissues A total of 485 primary PCa patients with RNA-seq data and clinical follow-up information were involved in the present study
Summary
Prostate cancer (PCa) is one of the most prevalent cancers that occur in men worldwide. Autophagyrelated genes (ARGs) may play an essential role in multiple biological processes of prostate cancer. ARGs expression signature has rarely been used to investigate the association between autophagy and prognosis in PCa. This study aimed to identify and assess prognostic ARGs signature to predict overall survival (OS) and disease-free survival (DFS) in PCa patients. Several studies reported that autophagy could play a role in tumor progression or tumor suppression in different stages of cancers [3, 4]. Prostate cancer (PCa) is a common malignancy of the urinary system and the second cause of cancerrelated death of males in western developed countries [5]. The majority of early-stage PCa patients have an excellent prognosis with a low mortality rate [7]. There are still a large number of PCa patients who develop the resistance to androgen deprivation therapy (ADT) and become castrationresistant PCa (CRPC), which results in a short survival time [8]
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