An endoplasmic reticulum stress-related signature featuring ASNS for predicting prognosis and immune landscape in prostate cancer

Prostate cancer (PRAD) is one of the common malignant tumors of the urinary system. In order to predict the treatment results for PRAD patients, this study proposes to develop a risk profile based on endoplasmic reticulum stress (ERS). Based on the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort and the Gene Expression Omnibus database (GSE70769), we verified the predictive signature. Using a random survival forest analysis, prognostically significant ERS-related genes were found. An ERS-related risk score (ERscore) was created using multivariable Cox analysis. In addition, the biological functions, genetic mutations and immune landscape related to ERscore are also studied to reveal the underlying mechanisms related to ERS in PRAD. We further explored the ERscore-related mechanisms by profiling a single-cell RNA sequencing (scRNA-seq) dataset (GSE137829) and explored the oncogenic role of ASNS in PRAD through in vitro experiments. The risk signature composed of eight ERS-related genes constructed in this study is an independent prognostic factor and validated in the MSKCC and GSE70769 data sets. The scRNA-seq data additionally revealed that several carcinogenic pathways were noticeably overactivated in the group with high ERS scores. As one of the prognostic genes, ASNS will significantly inhibit the proliferation, migration and invasion abilities of PRAD cells after its expression is interfered with. In conclusion, this study developed a novel risk-specific ERS-based clinical treatment strategy for patients with PRAD.