Journal Article

Pan-cancer profiling links C1orf50 to DNA repair and immune modulation in ovarian cancer

Rogachevskaya, Anna, Ohtsu, Akira, Otani, Yusuke, Arai, Seiji, Fujimura, Atsushi, Chin, Vanessa D., Toyooka, Shinichi, Peña, Tirso, Tanaka, Atsushi

2025

Overview

Background C1orf50 encodes a small, evolutionarily conserved protein, the function of which remains unclear. Its significance across various human cancers, particularly its specific role in ovarian cancer within an immunogenomic context, is not yet fully understood. Utilizing The Cancer Genome Atlas and single-cell RNA sequencing (scRNA-seq) public datasets, we conducted a comprehensive profiling of C1orf50 across multiple cancer types, with a particular focus on ovarian cancer, to investigate its associations with copy-number status, genomic instability, tumor programs, and the immune microenvironment. Results Across cancer types, copy-number gain or amplification of C1orf50 was most frequent in ovarian cancer and closely tracked with higher messenger RNA levels. Higher C1orf50 expression was associated with a greater tumor mutational burden and homologous recombination deficiency, as indicated by gene-set patterns that suggested heightened cell-cycle and cellular stress responses accompanied by reduced oxidative phosphorylation, enrichment of regulatory T cells, and depletion of resting memory CD4 T cells. In ovarian cancer, focal events at chromosome 1p34.2 were accompanied by stepwise increases in C1orf50 expression by clinical stage and were linked to higher tumor mutational burden, homologous recombination deficiency, and greater loss of heterozygosity, together with more frequent gene alterations in BRCA1 or BRCA2 . Immune composition clustered into profiles consistent with an immunosuppressive context in tumors with higher C1orf50 expression. The scRNA-seq data further revealed that cancer cells enhanced immune-suppressive interactions with various immune cell populations and diminished antigen-presentation signals. Analyses of genomic instability in ovarian cancer suggested mutational processes compatible with base-substitution patterns associated with cytidine deaminase activity and with insertion-deletion patterns characteristic of homologous recombination failure, while transcript-level patterns pointed to a broad downshift of canonical DNA repair activity with apparent compensatory adjustments in related pathways rather than a uniform change in any single pathway. Conclusions The overexpression of C1orf50 characterizes an aggressive immunogenomic phenotype in ovarian cancer, distinguished by genomic instability, impaired DNA repair mechanisms, and extensive immunosuppression. These findings indicate that C1orf50 warrants consideration as a potential biomarker and a prospective target for therapeutic investigation. Furthermore, they advocate for the progression to prospective validation and functional studies to ascertain its clinical significance.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Anopheles / Antigen presentation / Antigens / B cells / Biomarkers / BRCA1 protein / BRCA2 protein / Breast cancer / C1orf50 / Cancer / CD4 antigen / Cell cycle / Cellular stress response / Chromosome 1 / Cytidine deaminase / Datasets / DNA / DNA fingerprinting / DNA repair / DNA Repair - genetics / Female / Gene deletion / Gene expression / Genes / Genetic aspects / Genomes / Genomic Instability / Genomics / Gynecology / Heterozygosity / Humans / Immune evasion / Immune system / Immunological memory / Immunomodulation / Immunoregulation / Immunosuppression / Liver cancer / Loss of heterozygosity / Lymphocytes / Lymphocytes T / Medicine / Medicine & Public Health / Melanoma / Messenger RNA / Mutation / Ovarian cancer / Ovarian Neoplasms - genetics / Ovarian Neoplasms - immunology / Ovarian Neoplasms - pathology / Oxidative phosphorylation / Pan-cancer analysis / Phenotypes / Protein expression / Proteins / Reproductive Medicine / RNA sequencing / Skin cancer / T cells / Tumor microenvironment / Tumor Microenvironment - immunology / Tumors