Identification and validation of obesity related genes signature based on microenvironment phenotypes in prostate adenocarcinoma.

BACKGROUND

The role of obesity related genes (ORGs) in the immune checkpoint inhibitors (ICIs) treatment of prostate adenocarcinoma (PRAD) has not yet been proved by research.

METHODS

We comprehensively evaluated the ORGs patterns in PRAD based on tumor microenvironment (TME) phenotypes and immunotherapy efficacies. Then we constructed a ORGs risk score for prognosis and a ORGs signature for accurate prediction of TME phenotype and immunotherapy efficacy in order to evaluate individual patients.

RESULTS

Two distinct ORGs patterns were generated. The two ORGs patterns were consistent with inflammatory and non-inflammatory TME phenotypes. ORGs patterns had an important role for predicting immunotherapy efficacies. Next, we constructed a ORGs risk score for predicting each patient's prognosis with high performance in TCGA-PRAD. The ORGs risk score could be well verified in the external cohorts including GSE70769 and GSE21034. Then, we developed a ORGs signature and found it was significantly positively correlated with tumor-infiltrating lymphocytes in TCGA-PRAD. We found that each patient in the high-risk ORGs signature group represented a non-inflamed TME phenotype on the single cell level. The patients with high ORGs signature had more sensitivity to immunotherapy. And those ORGs were verified.

CONCLUSIONS

ORGs pattern depicts different TME phenotypes in PRAD. The ORGs risk score and ORGs signature have an important role for predicting prognosis and immunotherapy efficacies.