Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker in prostate cancer patients

Abstract

Abstract Purpose To explore the mechanisms that affect the radiosensitivity of prostate cancer and to search for radiotherapy outcome-related prognostic markers in prostate cancer patients through bioinformatics analysis. Methods The cancer cell data set GSE192817 and TCGA PRAD data set were downloaded from GEO database and UCSC Xena database for differential analysis, and biological function analysis of differential genes was performed (p < 0.05). Five gene sets were obtained from the MsigDB database, and ssGSEA and GSVA algorithms were used to quantitatively score cell line samples and patients. According to the expression of differential genes, the radiotherapy patients were divided into high and low expression groups for survival analysis, and the correlation between the expression of the prognostic gene SRXN1 and the GSVA score of oxidative stress response was analyzed. The differences between patients with high and low expression of SRXN1 were compared, and the patients were divided into two groups with high and low GSVA scores in response to oxidative stress and survival analysis was performed using the survival package. Results A total of six cancer cell lines after different radiotherapy treatment times were detected from GSE192817, and 114 differentially expressed genes were obtained, which were mainly related to nuclear membrane reassembly (p = 0.038) and cell adhesion (p = 0.042). Comparison of DNA damage-stimulated ssGSEA in different cell lines showed that, with the exception of the FaDu cell line, all cell lines treated with proton radiotherapy had higher response scores than those treated with X-ray radiotherapy. Comparing the three DNA damage-related functional GSVA results in TCGA PRAD patients showed that X-ray therapy had higher scores than patients without radiotherapy. Wilcoxon test screened 8 differential genes common to PC3 and DU145 cell lines. Survival analysis found that the high expression of TOR1B and SRXN1 was not conducive to the radiotherapy outcome of patients. Correlation analysis showed that SRXN1 gene expression was significantly negatively correlated with oxidative stress response GSVA score (PCC=-0.1536, p = 0.0003), and the oxidative stress response GSVA score was significantly higher in patients with low SRXN1 expression (p = 0.0072) ), high oxidative stress response scores in patients were beneficial to radiotherapy outcomes. Conclusions The prognostic marker SRXN1 of prostate cancer screened by bioinformatics plays an antioxidant stress role in prostate cancer cell lines after radiotherapy, which is associated with poor prognosis of radiotherapy outcomes in prostate cancer patients.