Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer
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Bingshu Xia1, Ming Shan1, Ji Wang1, Zhenbin Zhong1, Jingshu Geng2, Xiaohui He3, Tung Vu4, Dekai Zhang4, Da Pang1,5
1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China
2Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
3Department of Medical Records, Harbin Medical University Cancer Hospital, Harbin, 150081, China
4Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, 77030, USA
5Heilongjiang Academy of Medical Sciences, Heilongjiang Province, Harbin, 150086, China
Da Pang, email: [email protected]
Dekai Zhang, email: [email protected]
Keywords: breast cancer, DNA methylation, HOX genes, biomarker, prognosis
Received: April 12, 2016 Accepted: December 05, 2016 Published: December 25, 2016
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.
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