Details

Autor(en) / Beteiligte

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

Titel

MAL2 expression predicts distant metastasis and short survival in pancreatic cancer

Ist Teil von

• Surgery, 2013-09, Vol.154 (3), p.573-582

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.