Integrative Analysis of Genetic and Epigenetic Alterations in the CBX7 Gene Reveals Its Tumor-Suppressive Function by Regulating the Cell Cycle in Human Breast Cancer

Abstract

CBX7 is a member of the chromobox gene family, which plays an important role in epigenetic transcriptional regulation. In this study, we found that compared to normal mammary tissues, mRNA levels of CBX7 are consistently significantly downregulated in breast cancers (BCs) across different datasets. Integrative multiomics analysis revealed the genetic and epigenetic mechanisms for the loss of CBX7 expression in BCs. Lower expression levels of CBX7 are significantly associated with shorter overall, disease-free, and distant metastasis-free survival of patients with BC. These prognostic impacts of CBX7 are independent of estrogen receptor status and PAM50 molecular subtypes. Coexpression analysis identified 207 genes consistently coexpressed with CBX7 (157 negatively and 50 positively). Gene Ontology, KEGG, and Reactome enrichment analysis revealed that cell cycle‑, DNA replication‑, and mitosis-related pathways are significantly overrepresented within the set of CBX7 negatively coexpressed genes, suggesting that CBX7 functions as a suppressor of the cell cycle. Moreover, transcription factor enrichment analysis detected the E2F family of transcription factors significantly associated with CBX7 negatively coexpressed genes, consistent with E2F function regulating the cell cycle. Furthermore, we found that loss of CBX7 expression significantly increases genomic instability and tumor mutation burden. Our findings indicate that CBX7 acts as a tumor suppressor in BC through its potential role in the negative regulation of cell proliferation and the maintenance of genome integrity.