title: Expression profile of SIX family members correlates with clinic-pathological features and prognosis of breast cancer: A systematic review and meta-analysis.
abstract: Sineoculis homeobox homolog (SIX) family proteins, including SIX1, SIX2, SIX3, SIX4, SIX5, and SIX6, have been implicated in the initiation and progression of breast cancer, but the role of each member in breast tumor is not fully understood. We conducted a systematic review and meta-analysis to evaluate the association between the mRNA levels of all 6 members and clinic-pathological characteristics and clinical outcome of breast cancer patients based on the PRISMA statement criteria.ArrayExpress and Oncomine were searched for eligible databases published up to December 10, 2015. The association between the mRNA expression of SIX family members and clinic-pathological features and prognosis was measured by the odds ratio (OR), hazard ratio (HR), and the corresponding 95% confidence interval (CI), respectively. All statistical analyses were performed using STATA software.In total, 20 published Gene Expression Omnibus (GEO) databases with 3555 patients were analyzed. Our analysis revealed that patients with SIX1 overexpression had worse overall survival (OS) (HR: 1.28, 95% CI: 1.03-1.58) and shorter relapse-free survival (RFS) (HR: 1.28, 95% CI: 1.05-1.56), and much worse prognosis for luminal breast cancer patients with SIX1 overexpression (OS: HR: 1.64, 95% CI: 1.13-2.39; RFS: HR: 1.43, 95% CI: 1.06-1.93). We found that patients with higher SIX2 level had shorter time to both relapse and metastasis. However, high SIX3 mRNA level was a protective factor for OS and RFS of basal-like breast cancer patients.Our study suggested that members of SIX family played distinct roles in breast cancer. Detailed analysis of the expression of the SIX family members might provide useful information to predict breast cancer progression and prognosis.
authors.affiliation: Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Nursing School of Pingdingshan University, Pingdingshan, Henan Clinical Research Center, Wuhan Medical and Healthcare Center for Women and Children, Wuhan, Hubei, People's Republic of China Departments of Oncology and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI.
authors.forename: Han-Xiao
authors.initials: HX
authors.lastname: Xu
authors.forename: Kong-Ju
authors.initials: KJ
authors.lastname: Wu
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Tian
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Na
authors.initials: N
authors.lastname: Han
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: He
authors.forename: Xun
authors.initials: X
authors.lastname: Yuan
authors.forename: Gen Sheng
authors.initials: GS
authors.lastname: Wu
authors.forename: Kong-Ming
authors.initials: KM
authors.lastname: Wu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005136:Eye Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D009419:Nerve Tissue Proteins; D011379:Prognosis; D015534:Trans-Activators; D000097607:Homeobox Protein SIX3
chemical_list: D014408:Biomarkers, Tumor; D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; D000097607:Homeobox Protein SIX3; C099236:SIX1 protein, human; C484762:SIX2 protein, human; C490851:SIX4 protein, human; C106687:SIX5 protein, human; C491945:SIX6 protein, human