Clinical relevance of ORCs in predicting prognosis and immunotherapy outcomes: A pan-cancer analysis

Abstract

Background: The origin recognition complex (ORC) consists of six subunits and mediates DNA replication by binding to its origin. Recent studies show that ORCs are closely related to various biological processes in tumors. However, a comprehensive study of ORCs in pan-cancer has not been conducted.

Results: A systematic evaluation of the expression, mutation, and prognostic significance of ORCs was conducted across cancer types using data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The single-sample Gene Set Enrichment Analysis (ssGSEA) was performed using R package "Gene Set Variation Analysis (GSVA)" to evaluate ORC score. ORC score was significantly elevated in most cancers and linked with an inferior prognosis. It was positively related to the G2/M checkpoint and DNA repair pathways. An elevated ORC score also correlated with tumor mutation burden (TMB)/ microsatellite instability (MSI). A prognosis analysis suggested that high ORC scores were associated with heightened immunotherapeutic sensitivity.

Conclusions: Our research elucidates the genomic changes associated with and clinical relevance of ORCs in cancer and provides unique insights for future investigation of ORCs in immunotherapy.

Keywords: Cancer; Immunotherapy; MSI; ORC; Prognosis; TMB.