Prognostic and immunological role of MRC1: A pan-cancer analysis

Abstract MRC1 is an endocytic lectin receptor primarily expressed in macrophages, dendritic cells and some endothelial cells. It acts as phagocytic receptor for bacteria, fungi and other pathogens. Until now, the role of MRC1 in cancer remains unclear. We performed a pan-cancer analysis to investigate the potential value of MRC1 in cancer immunotherapy. MRC1 expression in normal tissues, cancer cell lines, and tumor tissue compared with their para-cancerous tissues displayed heterogeneity among different cancers. By analyzing the correlation between prognostic value and expression of MRC1 in multiple cancer types, we found that MRC1 levels significantly affected prognosis in the seven cancer types. High MRC1 expression was associated with poorer prognosis in six types of cancers and improved prognosis of GBM, KICH, LAML, LUSC, THCA, and THYM. Then we compared these results with immune-related indicators including immune infiltrative cells, immune scores, and immune checkpoint molecules. MRC1 expression significantly correlated with the 6 immune infiltrates in most cancer types. Similarly, MRC1 was also positively correlated with Stromal score, Immune score, and ESTIMATE score. These results indicate that MRC1 affects prognosis through immune related pathways. For immune related molecules, MRC1 was both significantly associated with stimulatory and inhibitory checkpoint molecules, which suggest that the role of MRC1 in immune system differs from cancer types. To explore whether MRC1 has a predictive value in the efficacy of immune checkpoint inhibitors (ICIs) treatment, we analyzing the relationship between current predictors and MRC1 in multiple cancer types. MRC1 expression was positively correlated with tumor mutation burden (TMB) and DNA mismatch repair (MMR) genes in most of cancer types but negatively associated with a small proportion of cancer types. However, MRC1 expression was negatively correlated with tumor neoantigen burden (TNB) and microsatellite instability (MSI) in most of cancer types. The relationship between MRC1 and the four DNA methyltransferases was significant in multiple cancers types, but also with a cancer type-specific pattern. In conclusion, our study finds that MRC1 expression correlates with a variety of tumors and its prognostic value in multiple cancer types. In addition, the expression of MRC1 has a potential predictive value for the efficacy of ICIs. Nevertheless, in practical application, it needs to be adjusted according to different cancer types.