Comprehensive analysis of the biological functions of endoplasmic reticulum stress in prostate cancer

Introduction: Endoplasmic reticulum stress (ERS) has sizeable affect on cancer proliferation, metastasis, immunotherapy and chemoradiotherapy resistance. However, the effect of ERS on the biochemical recurrence (BCR) of prostate cancer patients remains elusive. Here, we generated an ERS-related genes risk signature to evaluate the physiological function of ERS in PCa with BCR.

Methods: We collected the ERS-related genes from the GeneCards. The edgeR package was used to screen the differential ERS-related genes in PCa from TCGA datasets. ERS-related gene risk signature was then established using LASSO and multivariate Cox regression models and validated by GEO data sets. Nomogram was developed to assess BCR-free survival possibility. Meanwhile, the correlations between ERS-related signature, gene mutations, drug sensitivity and tumor microenvironment were also investigated.

Results: We obtained an ERS risk signature consisting of five genes (AFP, COL10A1, DNAJB1, EGF and PTGS2). Kaplan Meier survival analysis and ROC Curve analysis indicated that the high risk score of ERS-related gene signature was associated with poor BCR-free prognosis in PCa patients. Besides, immune cell infiltration and immune checkpoint expression levels differed between high- and low-risk scoring subgroups. Moreover, drug sensitivity analyzed indicated that high-risk score group may be involved in apoptosis pathway.

Discussion: This study comprehensively analyzed the characteristics of ERS related genes in PCa, and created a five-gene signature, which could effectively predict the BCR time of PCa patients. Targeting ERS related genes and pathways may provide potential guidance for the treatment of PCa.