Xia Bingshu, Shan Ming, Wang Ji, Zhong Zhenbin, Geng Jingshu, He Xiaohui, Vu Tung, Zhang Dekai, Pang Da
Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Oncotarget. 2017 Feb 7;8(6):9794-9805. doi: 10.18632/oncotarget.14216.
Homeobox A11 (HOXA11) is one of the hypermethylated genes in breast cancer and its function in breast tumorigenesis remains elusive. In this study, we analyzed the methylation status of HOXA11 in 264 paired breast cancer and normal tissue as well as in matched serum samples by MethyLight assay. Further, the function of HOXA11 in breast tumorigenesis was analyzed by cell proliferation and migration assays. We found that HOXA11 was hypermethylated in cancer tissues (45.08%), especially in invasive ductal carcinomas (P<0.001), patients with a family history of cancer (P=0.033), cases with metastatic lymph nodes (P=0.004) and P53 positive group (P=0.017). Kaplan-Meier survival analysis and Cox regression analysis revealed that HOXA11 hypermethylation is an independent predictor of poor outcomes. The over expression of HOXA11 suppressed cell growth in MDA-MB-231, MCF7, SKBR3 and BT474 cells. In conclusion, the hypermethylation of HOXA11 is an independent prognostic biomarker in breast cancer. Additionally, HOXA11 can be a potential tumor suppressor.
同源框A11（HOXA11）是乳腺癌中发生高甲基化的基因之一，其在乳腺肿瘤发生中的作用仍不清楚。在本研究中，我们通过甲基化荧光定量分析（MethyLight分析）检测了264对乳腺癌组织和正常组织以及配对血清样本中HOXA11的甲基化状态。此外，通过细胞增殖和迁移试验分析了HOXA11在乳腺肿瘤发生中的作用。我们发现HOXA11在癌组织中存在高甲基化（45.08%），尤其是在浸润性导管癌中（P<0.001）、有癌症家族史的患者中（P=0.033）、有淋巴结转移的病例中（P=0.004）以及P53阳性组中（P=0.017）。Kaplan-Meier生存分析和Cox回归分析显示，HOXA11高甲基化是预后不良的独立预测因素。HOXA11的过表达抑制了MDA-MB-231、MCF7、SKBR3和BT474细胞的生长。总之，HOXA11的高甲基化是乳腺癌独立的预后生物标志物。此外，HOXA11可能是一种潜在的肿瘤抑制因子。
