title: MAL2 expression predicts distant metastasis and short survival in pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cancer is associated with a devastating prognosis, partially because of its aggressive metastatic ability. Identification of prognostic markers of metastasis would be useful in the clinical management of postoperative patients with pancreatic cancer. Mal, T-cell differentiation protein 2 (MAL2) has been identified as a molecule predictive of metastases; the clinical relevance of MAL2 in pancreatic cancer is unknown.
  
  
  METHODS
  Orthotopic human pancreatic cancer xenografts from the pancreatic cancer cell line SUIT-2 were established in nude mice. Only liver metastasis was harvested and cultured. These metastatic cycles were repeated 5 times to establish a highly metastatic cell line, termed metastatic SUIT-2 (MS). We investigated proliferation and motility of MS cells compared with those of the parent SUIT-2. Microarray analysis was performed to investigate differences in gene expression. We also performed immunohistochemical analysis of 89 formalin-fixed, paraffin-embedded human pancreatic cancer tissue samples to investigate the clinical significance of MAL2 expression.
  
  
  RESULTS
  MS cells showed a greater metastatic rate after orthotopic implantation than parental SUIT-2. MS cells had increased motility but decreased proliferation compared with parental SUIT-2. Microarray analyses showed that 26 genes were significantly upregulated (>10-fold) in MS cells compared with parental SUIT-2, particularly MAL2 expression. Immunohistochemical analysis showed that high expression of MAL2 was associated with a lesser survival of postoperative patients (P = .03) and a high rate of distant metastasis (P = .008).
  
  
  CONCLUSIONS
  We characterized a newly established pancreatic cancer cell line with highly metastatic potential. MAL2 is a promising predictive marker for distant metastasis and short survival in patients with resected pancreatic cancer.
authors.affiliation: Department of Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Eguchi
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Shingo
authors.initials: S
authors.lastname: Kozono
authors.forename: Naoki
authors.initials: N
authors.lastname: Ikenaga
authors.forename: Koji
authors.initials: K
authors.lastname: Shindo
authors.forename: Lin
authors.initials: L
authors.lastname: Cui
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujiwara
authors.forename: Shin
authors.initials: S
authors.lastname: Akagawa
authors.forename: Takao
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Takahata
authors.forename: Shoji
authors.initials: S
authors.lastname: Tokunaga
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Mizumoto
authors.forename: Masao
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000032:analysis* / Q000235:genetics; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; C438606:MAL2 protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins