title: Homeobox A11 hypermethylation indicates unfavorable prognosis in breast cancer.
abstract: 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.
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Bingshu
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shan
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Medical Records, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: He
authors.affiliation: Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, 77030, USA.
authors.forename: Tung
authors.initials: T
authors.lastname: Vu
authors.affiliation: Center for Infectious and Inflammatory Diseases, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, 77030, USA.
authors.forename: Dekai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, China.|Heilongjiang Academy of Medical Sciences, Heilongjiang Province, Harbin, 150086, China.
authors.forename: Da
authors.initials: D
authors.lastname: Pang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D002465:Cell Movement; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D040941:Heredity; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008875:Middle Aged; D010375:Pedigree; D016016:Proportional Hazards Models; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C484298:HOXA11 protein, human; D018398:Homeodomain Proteins
keywords: DNA methylation; HOX genes; biomarker; breast cancer; prognosis