title: Sineoculis homeobox homolog 1 protein overexpression as an independent biomarker for pancreatic ductal adenocarcinoma.
abstract: Sineoculis homeobox homolog 1 (SIX1) is a member of the SIX gene family. It is highly expressed in cancers derived from tissues that play a fundamental role during embryogenesis. Recent studies suggest that inappropriate expression of SIX1 can both initiate tumorigenesis and promote metastasis. To investigate the clinicopathological significance of SIX1 expression in pancreatic ductal adenocarcinoma (PDAC), and to further identify its role as a potential biomarker and therapeutic target in PDAC, 103 PDAC tissue samples and 45 normal pancreatic tissue samples were immunohistochemically stained for SIX1 protein. The localization of SIX1 protein was detected in Panc-1 cancer cells using immunofluorescence staining. Correlations between SIX1 overexpression and the clinicopathological features of pancreatic cancer were evaluated using Chi-square (χ(2)) tests, differences in survival curves were analyzed using log-rank tests, and multivariate survival analysis was performed using the Cox proportional hazard regression model. In results, SIX1 protein showed mainly cytoplasmic/perinuclear staining pattern in PDAC with immunohistochemistry. The strongly positive rate of SIX1 protein was 60.2% (62/103) in PDAC, which was significantly higher than normal pancreatic tissue (6.7%, 3/45). SIX1 overexpression was positively correlated with tumor size, TNM stage, lymph node metastasis, and grade of PDAC (P < 0.001). SIX1 high expression levels influenced overall survival rates in G1, G2, stage I-II and stage III-IV groups of PDAC; and high expression levels had significantly lower overall survival rates than SIX1 low expression levels. In conclusion, SIX1 emerged as a significant independent prognostic factor in PDAC. SIX1 overexpression appears to be associated with PDAC, and may be a potential biomarker for early diagnosis and prognostic evaluation of PDAC.
authors.affiliation: Key Laboratory of Changbai Mountain Biological Resources and Functional Molecule, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Internal Medicine, Yanbian University Hospital, Yanji 133000, China.. Electronic address: drjinah@163.com.
authors.forename: Aihua
authors.initials: A
authors.lastname: Jin
authors.affiliation: Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China. Electronic address: xuyunjie87@163.com.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China. Electronic address: liushs@ybu.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Key Laboratory of Changbai Mountain Biological Resources and Functional Molecule, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China. Electronic address: jintf@ybu.edu.cn.
authors.forename: Tiefeng
authors.initials: T
authors.lastname: Jin
authors.affiliation: Key Laboratory of Changbai Mountain Biological Resources and Functional Molecule, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China. Electronic address: lizh@ybu.edu.cn.
authors.forename: Zhuhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, Yanbian University Hospital, Yanji 133000, China.. Electronic address: jinhyyj@msn.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China; Department of Medical Imaging, Eastern Liaoning University Medical College, Dandong 118002, China. Electronic address: linlijuan3066@sina.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Lin
authors.affiliation: Key Laboratory of Changbai Mountain Biological Resources and Functional Molecule, Ministry of Education, Yanbian University, Yanji 133002, China; Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China. Electronic address: zhlin720@ybu.edu.cn.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C099236:SIX1 protein, human
keywords: Biomarker; Pancreatic ductal adenocarcinoma; Sineoculis homeobox homolog 1; Survival rate