Establishment of a novel efferocytosis potential index predicts prognosis and immunotherapy response in cancers

Abstract

The biological function and prognostic value of efferocytosis in cancer remains unclear. In this study, we systematically analysed the expression profiles and genetic variations of 50 efferocytosis-related regulator genes in 33 cancer types. Using data from The Cancer Genome Atlas, we established an efferocytosis potential index (EPI) model to represent the efferocytosis level in each cancer type. The relationship between the EPI and prognosis, immune-related molecules, specific pathways, and drug sensitivity was determined. We found that efferocytosis regulator genes were abnormally expressed in cancer tissue, perhaps owing to copy number variations, gene alterations, and DNA methylation. For the most part, the EPI was higher in tumour vs. normal tissues. In most of the 33 cancer types, it positively correlated with cell death- and immune-related pathway enrichment, the tumour microenvironment, immune infiltration, and drug sensitivity. For specific cancers, a high EPI may be a prognostic risk factor and, in patients treated receiving immune checkpoint therapy, a predictor of poor prognosis. Our study reveals the biological functions of efferocytosis-related regulator genes in distinct cancers and highlights the potential of efferocytosis intervention in cancer therapy.