Department of Gastrointestinal Surgery, Hunan Provincial People's Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410005, Hunan, China.
Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha 410008, Hunan, China.
Aging (Albany NY). 2022 Aug 17;14(16):6579-6593. doi: 10.18632/aging.204231.
Breast cancer is the most common lethal carcinoma worldwide and better targeted therapies are still worthy of exploration, having had some great successes already. Abnormal expression of ALKBH members were found in various cancers, and the roles played by it were the focus of attention. The ALKBH gene family encodes nine homologous enzymes (ALKBH1-8 and FTO) to repair DNA or RNA depending on Fe2+ and α-ketoglutarate (α-KG), which is related to carcinogenesis. In this study, we applied several databases to explore the roles of ALKBHs in breast cancer. We found that ALKBH members were abnormal expression in breast cancer and associated with tumor stage and subclasses. Higher alteration rates of ALKBH family were found in breast cancer. Function enrichment revealed that several cancer-associated signal pathways were related to ALKBH family such as PI3K-Akt signaling pathway and axon guidance. Infiltration of immune cells (Eosinophiles, NK CD56bright cells, mast cells, T helper cells and so on) were strongly related to ALKBHs. Moreover, we further found that there was strong correlation between ALKBH7 and higher age, later T stage, ER/PR positive and post-menopause of breast cancer patients, and patients with higher ALKBH7 expression had shorter overall survival (OS) and post progression survival (PPS). In conclusion, our findings may provide novel insights into ALKBH-targeted therapy for breast cancer patients, and ALKBH7 may be a potential prognostic biomarker.
乳腺癌是全球最常见的致命性癌种,更好的靶向治疗方法仍值得探索,因为已经取得了一些重大成功。已经发现 ALKBH 成员在各种癌症中异常表达,其发挥的作用引起了关注。ALKBH 基因家族编码九个同源酶(ALKBH1-8 和 FTO),根据 Fe2+和α-酮戊二酸(α-KG)修复 DNA 或 RNA,这与癌症的发生有关。在本研究中,我们应用了几个数据库来探索 ALKBHs 在乳腺癌中的作用。我们发现 ALKBH 成员在乳腺癌中异常表达,并与肿瘤分期和亚型有关。乳腺癌中 ALKBH 家族的改变率较高。功能富集表明,几种与癌症相关的信号通路与 ALKBH 家族有关,如 PI3K-Akt 信号通路和轴突导向。免疫细胞(嗜酸性粒细胞、NK CD56bright 细胞、肥大细胞、辅助性 T 细胞等)的浸润与 ALKBHs 密切相关。此外,我们还发现 ALKBH7 与较高的年龄、较晚的 T 期、ER/PR 阳性和绝经后状态以及 ALKBH7 表达较高的患者的总生存期(OS)和无进展生存期(PPS)较短之间存在很强的相关性。总之,我们的研究结果可能为 ALKBH 靶向治疗乳腺癌患者提供新的思路,ALKBH7 可能是一个有潜力的预后生物标志物。