title: The clinical significance of SWI/SNF complex in pancreatic cancer.
abstract: Chromatin remodeling factors have been the subject of great interest in oncology. However, little is known about their role in pancreatic cancer. The objective of this study was to clarify the clinical significance of the SWItch/sucrose non-fermentable (SWI/SNF) complex in patients with pancreatic cancer. A total of 68 patients with pancreatic cancer who underwent R0, 1 resection were enrolled. Cancer tissues were processed to tissue microarray, then stained immunohistochemically by using antibody of SWI/SNF components; BRM, BRG1, BAF250a, BAF180 and BAF47. The correlation of expression levels and clinicopathological outcomes were analyzed, followed by the multivariate analysis of prognostic factors for overall survival. The expression levels of the SWI/SNF components were categorized as low or high according to the median value of Histoscore. Statistical analysis revealed that BRM expression was related to tumor size, T factor, M factor, lymphatic invasion and stage BRG1 expression to histology and stage BAF180 expression to tumor size and BAF47 expression to lymphatic invasion, respectively. Multivariate Cox proportional hazard analysis showed that high BRM and low BAF180 expression levels were independent predictors of worse survival in patients with pancreatic cancer. High BRM, and low BAF180 were also independent prognostic factors for poor survival in the subgroup with adjuvant gemcitabine. These results suggest that the specific cofactors of SWI/SNF chromatin remodeling complex certainly have roles in pancreatic cancer. High BRM, and low BAF180 are useful biomarkers for poor prognosis in pancreatic cancer.
authors.affiliation: Department of Gastroenterological Surgery, Kanagawa Cancer Center, Asahi-ku, Yokohama, Kanagawa 241-0815, Japan. masakatsunumata@hotmail.co.jp
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Numata
authors.forename: Soichiro
authors.initials: S
authors.lastname: Morinaga
authors.forename: Takuo
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamagawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Manabu
authors.initials: M
authors.lastname: Shiozawa
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kameda
authors.forename: Shinichi
authors.initials: S
authors.lastname: Okawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Rino
authors.forename: Makoto
authors.initials: M
authors.lastname: Akaike
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D004265:DNA Helicases / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis; D010190:Pancreatic Neoplasms; D000071796:SMARCB1 Protein; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000096:biosynthesis*
chemical_list: C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C102195:PBRM1 protein, human; C084011:SMARCA2 protein, human; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases