CCNA2 Is a Prognostic Biomarker for ER+ Breast Cancer and Tamoxifen Resistance

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.

精准识别有效的预后生物标志物与治疗靶点，对于雌激素受体阳性（ER+）乳腺癌的临床管理具有至关重要的意义。CCNA2（亦称CyclinA2）属于高度保守的细胞周期蛋白家族，在多种癌症类型中均呈现显著过表达。本研究证实，CCNA2对ER+乳腺癌患者的无远处转移生存期、无病生存期、无复发生存期及总生存期均具有显著的预测价值。本研究同时发现，CCNA2与他莫昔芬耐药性密切相关。此外，基因集富集分析（Gene Set Enrichment Analysis, GSEA）结果显示，CCNA2的表达水平与内分泌治疗耐药样本中的过表达基因呈正相关。最后，通过构建CCNA2-药物相互作用网络，本研究明确了CCNA2与多款已上市抗肿瘤药物之间的相互作用。综上，本研究表明CCNA2可作为ER+乳腺癌预后评估及他莫昔芬疗效监测的生物标志物，同时也是开发新型策略以预防乃至逆转他莫昔芬耐药的潜在治疗靶点。此外，CCNA2的表达水平可辅助他莫昔芬疗效监测，并为个性化治疗方案的制定提供指导。然而，在将其应用于临床实践之前，仍需开展体内外实验及多中心随机对照临床试验。