Cuproptosis-related genes affect the prognosis of prostate cancer by potentially regulating the immune microenvironment

Abstract

Abstract Purpose As a novel form of cell death, cuproptosis has been found to have an effect on the occurrence, development and prognosis of many other carcinomas, such as renal clear cell carcinoma, hepatocellular carcinoma and breast cancer. However, the role of cuproptosis in prostate cancer is poorly understood. Methods We retrieved and downloaded gene expression profiles and clinical information from public databases. We used unsupervised clustering to find differences in the immune microenvironment between subgroups and then obtained the immune differential genes between subgroups. Based on the random forest machine learning algorithm, we constructed a model to distinguish patients’ outcomes and verified their predictive efficacy. Gene with potential regulatory effects was further selected and validated experimentally. Results From our findings, most of the cuproptosis-related genes were differentially expressed between prostate cancer and tumor-adjacent tissues. Two clusters based on consensus cluster analysis of cuproptosis-related genes expression showed different clinical information and immune microenvironment. We used random forest as the core algorithm to screen prognostic relevant cuproptosis immune-related genes and constructed a risk stratification model. Different risk groups predicted by the model presented different clinicopathological stages and prognosis. Subsequent experiments revealed that inhibition of PROK1 expression promoted prostate cancer cell proliferation and invasion, and overexpression of PROK1 gave the opposite result, validating the anticancer effect of PROK1 and its potential to become a novel therapeutic target. Conclusion Our study reveals a landscape of cuproptosis-related genes in prostate cancer that may influence prostate cancer progression by modulating immunity. One of the key genes, PROK1, was found to be an oncogene. Our study provides new ideas about the immune environment of prostate cancer.