Pan-cancer analysis of polycomb repressive complex 1 (PRC1) in relation to prognosis and immunotherapy response.

Abstract

Introduction: Polycomb repressive complex 1 (PRC1) is a crucial epigenetic modification complex that plays significant roles in embryonic development, cell differentiation, and tumorigenesis. However, its predictive value and role in immunotherapy remain unclear.

Material and methods: Expression of the PRC1 complex was analyzed through RNA-seq, quantitative PCR, and immunohistochemistry. Then, we utilized the TCGA and GEO databases to cross-validate the prognostic risk. A pan-cancer analysis was conducted, including clinical traits, tumor microenvironment (TME), tumor mutational burden (TMB), stemness indices, and drug sensitivity. Furthermore, we cross-validated the effect of PRC1 on immunotherapy through ROC Plotter and Kaplan-Meier Plotter databases. The immune cell infiltration and signaling pathways were further identified.

Results: The expression of PRC1 differed between tumor and normal tissue in most cases. In particular, the whole group exhibited consistent high abundance in gastric, colorectal, and liver cancer. In addition, the expression of PRC1 can serve as a marker of survival prognosis. The members of PRC1 were also associated with clinical characteristics, immune cell infiltration, immune checkpoint inhibitor (ICI)-related immune indexes, and drug sensitivity. Moreover, high expression of BMI1 can increase resistance to immunotherapy, with a worse prognosis. The expression level of BMI1 can affect the immune-related pathways, as indicated by the gene set enrichment analysis (GSEA).

Conclusions: Our study revealed the expression, prognostic value and mechanism of PRC1 in pan-cancer. Its core member BMI1 can be used as a biomarker for the prognosis of tumor patients and the efficacy of ICIs. It provides a theoretical basis for the implementation of individualized immunotherapy.