title: CCNA2 is a prognostic biomarker for ER+ breast cancer and tamoxifen resistance.
abstract: Identification of effective prognostic biomarkers and targets are of crucial importance to the management of estrogen receptor positive (ER+) breast cancer. CCNA2 (also known as CyclinA2) belongs to the highly conserved cyclin family and is significantly overexpressed in various cancer types. In this study, we demonstrated that CCNA2 had significant predictive power in distant metastasis free survival, disease free survival, recurrence free survival and overall survival of ER+ breast cancer patients. We also found that CCNA2 was closely associated with tamoxifen resistance. In addition, gene set enrichment analysis (GSEA) revealed that its expression was positively associated with genes overexpressed in endocrine therapy resistant samples. Finally, though CCNA2-Drug interaction network, we demonstrated the interactions between CCNA2 and several available cancer drugs. Overall, we suggest that CCNA2 is a biomarker for the prognosis of ER+ breast cancer and monitoring of tamoxifen efficacy. It's also a promising target for developing new strategies to prevent or even reverse tamoxifen resistance. Moreover, CCNA2 expression may help monitoring tamoxifen efficacy and directing personalized therapies. Nevertheless, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed before its application in clinical settings.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Gao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Orthopedics, Renmin Hospital, Wuhan University, Wuhan, Hubei, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Ao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D056751:Cyclin A2 / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C503721:CCNA2 protein, human; D056751:Cyclin A2; D011960:Receptors, Estrogen; D013629:Tamoxifen