Data-Driven Discovery of a Key Regulator Cyclin A2 as a Promising Therapeutic Target in Hormone-Sensitive Cancers.

Hormone-sensitive cancers (HSCs) are one of the predominant types of cancer leading to death globally. The current study has attempted to discover a potential therapeutic target that could be used against HSCs in women, namely, breast, ovarian, and endometrial cancer. The differentially expressed genes in each cancer type were compared with previously reported tamoxifen resistance-causing genes. The hub genes CCNA2, CDCA8, ISG15, and E2F1 were found in breast cancer, CCNA2, CDCA8, CXCR4, and LYN were found in ovarian cancer, and CCNA2 and POLE2 were found in endometrial cancer. The clusters with the hub genes were screened for functional importance and were found to be significant in cell cycle regulation pathways. The expression significance, correlation, mutational profile, survival potency, treatment response status, and clinical profile revealed that CCNA2 was significantly associated with all three cancers. This study revealed that CCNA2 was positively correlated with other resistance-causing genes such as CENPE, MK167, CDCA8, NEK2, PRC1, ZWINT, CDKN3, MYBL2, and E2F1, in various cancers, validating its potential to cause resistance. Compared with other hub genes, CCNA2 had a Lower mutation percentage and critical hazard ratios of 2.16, 1.75, and 1.68 in breast, ovarian, and endometrial cancers, respectively, indicating its pivotal role in survival. The median CCNA2 expression level was 21.301 in stage IV BC patients, 38.481 in stage II ovarian cancer patients, and 23.206 in stage IV endometrial cancer patients. Thus, CCNA2 could be a potential therapeutic target for treating HSCs with endocrine therapy resistance.