An antibody-dependent cellular phagocytosis-related gene signature predicts survival and response to immunotherapy in stomach adenocarcinoma.

Abstract

Antibody-dependent cellular phagocytosis (ADCP) is an immune biological process and plays a biological role in the clearance of tumor cells and the response to immune checkpoint inhibitors. However, the effects of ADCP on stomach adenocarcinoma (STAD) remain unclear. Clinical and genomic data were extracted from multiple datasets. The ADCP-related signature was established using Cox least absolute shrinkage and selection operator regression. Expression of the C5a receptor also known as complement component 5a receptor 1 in the tumor and adjacent-normal tissues was calculated using immunohistochemistry staining. Validation of the signature was conducted in the training and validation cohorts by Cox regression and log-rank tests. Furthermore, the immune infiltrates, the tumor immune dysfunction and exclusion score, and tumor mutation burden score were calculated using the corresponding algorithms, and Mann-Whitney U tests were used to evaluate the differences between groups. Seventy-three hub genes with predictive performance were identified to establish an ADCP-related signature. Accordingly, a 27-gene signature was established, C5a receptor also known as complement component 5a receptor 1, one of the signature genes, had higher expression in tumors than adjacent-normal samples, and its predictive performance was validated in the GSE84437 and The Cancer Genome Atlas cohorts. We found that the ADCP-related signature is an excellent prognostic predictor of STAD. Moreover, the molecular characteristics and some indices of response to immunotherapy differed between the high- and low-risk groups. We constructed a 27-gene signature that is associated with the prognosis and response to STAD-based immunotherapy and provide insights into the biological mechanisms underlying this predictive function.