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Abstract

Volume 25, Issue 2 (March 2023) 25, 208–216; 10.4103/aja202281

An autophagy-related gene prognostic index predicting biochemical recurrence, metastasis, and drug resistance for prostate cancer

Wei-Zhen Zhu, De-Chao Feng, Qiao Xiong, Xu Shi, Fa-Cai Zhang, Qiang Wei, Lu Yang

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu 610041, China

Correspondence: Dr. Q Wei (weiqiang933@126.com) or Dr. L Yang (wycleflue@163.com)

Date of Submission 21-Mar-2022 Date of Acceptance 20-Sep-2022 Date of Web Publication 11-Nov-2022

Abstract

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23–9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89–26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07–2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16–2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = −0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.

Keywords: autophagy; biochemical recurrence; immune checkpoint; metastasis-free survival; prostate cancer; tumor immune microenvironment

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Asian Journal of Andrology CN 31-1795/R ISSN 1008-682X  Copyright © 2023  Shanghai Materia Medica, Chinese Academy of Sciences.  All rights reserved.