MAL2 expression predicts distant metastasis and short survival in pancreatic cancer

Daiki Eguchi, Kenoki Ohuchida, Shingo Kozono, Naoki Ikenaga, Koji Shindo, Lin Cui, Kenji Fujiwara, Shin Akagawa, Takao Ohtsuka, Shunichi Takahata, Shoji Tokunaga, Kazuhiro Mizumoto, Masao Tanaka

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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). Conclusion: 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.

Original languageEnglish
Pages (from-to)573-582
Number of pages10
JournalSurgery (United States)
Volume154
Issue number3
DOIs
Publication statusPublished - Sep 1 2013

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All Science Journal Classification (ASJC) codes

  • Surgery

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