MAL2 expression predicts distant metastasis and short survival in pancreatic cancer
MAL2 expression predicts distant metastasis and short survival in pancreatic cancer
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DOI：
10.1016/j.surg.2013.03.010
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发表时间：
2013-09-01
期刊：
影响因子：
3.8
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Eguchi, Daiki;Ohuchida, Kenoki;Tanaka, Masao
背景。胰腺癌预后不良，部分原因是其具有侵袭性转移能力。鉴别胰腺癌转移的预后指标对胰腺癌术后患者的临床治疗有重要意义。t细胞分化蛋白2 （MAL2）已被确定为预测转移的分子；MAL2在胰腺癌中的临床意义尚不清楚。在裸鼠体内建立了人胰腺癌西服-2细胞系的原位异种移植物。只采集并培养肝转移灶。这些转移周期重复5次以建立高转移细胞系，称为转移SUIT-2 （MS）。我们比较了MS细胞与亲本西服-2的增殖和运动。微阵列分析研究基因表达的差异。我们还对89例福尔马林固定石蜡包埋的人胰腺癌组织样本进行了免疫组织化学分析，以探讨MAL2表达的临床意义。原位移植后MS细胞的转移率高于亲代的SUIT-2。与亲本西服-2相比，MS细胞运动性增加，但增殖能力下降。微阵列分析显示，与亲代SUIT-2相比，MS细胞中有26个基因显著上调（>10倍），尤其是MAL2的表达。免疫组化分析显示，MAL2高表达与术后患者生存率低（P = 0.03）和远处转移率高（P = 0.008）相关。我们描述了一个新建立的具有高度转移潜力的胰腺癌细胞系。MAL2是胰腺癌切除术患者远处转移和短期生存的一个有希望的预测标志物。
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.