Serum REG4 Level Is a Predictive Biomarker for the Response to Preoperative Chemoradiotherapy in Patients With Pancreatic Cancer
Serum REG4 Level Is a Predictive Biomarker for the Response to Preoperative Chemoradiotherapy in Patients With Pancreatic Cancer
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DOI：
10.1097/mpa.0b013e3181ac5337
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发表时间：
2009-10-01
期刊：
影响因子：
2.9
通讯作者：
Nakagawa, Hidewaki
中科院分区：
文献类型：
--
作者：
Eguchi, Hidetoshi;Ishikawa, Osamu;Nakagawa, Hidewaki
目的：术前放化疗是提高胰腺癌生存率的关键策略之一;然而，尚未建立预测反应的方法。本研究的目的是前瞻性地评估REG 4的预测价值，一个新的成员的再生（REG）胰岛衍生的家族proteins.Methods：稳定REG 4-表达细胞建立从胰腺癌细胞系和暴露在体外γ射线或吉西他滨调查REG 4的相关性，化疗或放疗的抵抗。在23例可切除的胰腺癌患者中，术前测定血清REG 4浓度，术后评价组织学反应。结果：一个3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑（MTT）测定和荧光激活细胞扫描（FACS）显示REG 4过表达细胞对γ-但对吉西他滨显示出适度的耐药性。REG 4水平较高的患者，而不是癌胚抗原或CA-19-9，显示出对放化疗的不利组织学反应（斯皮尔曼，rho = 0.439，P = 0.039）。显示出较高的REG 4水平的患者经历了局部复发postoperatives.Conclusions：这些数据表明，在体外和体内，REG 4蛋白过表达与术前放化疗的不利反应。REG 4在临床上可用作预测性生物标志物。
Objectives: Preoperative chemoradiotherapy is one of the key strategies for the improvement of survival in pancreatic cancer; however, no method to predict the response has yet been established. The aim of this study was to prospectively evaluate the predictive value of REG4, a new member of the regenerating (REG) islet-derived family of proteins.Methods: Stably REG4-expressing cells were established from a pancreatic cancer cell line and exposed in vitro to gamma-ray or gemcitabine to investigate the relevance of REG4 to the resistance to chemotherapy or radiotherapy. In 23 patients with resectable pancreatic cancer, the serum concentration of REG4 was measured before preoperative chemoradiotherapy, and the histologic response was evaluated after the surgery.Results: A 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and fluorescence activated cell scanning (FACS) revealed that REG4-overexpressing cells were resistant to gamma-radiation but showed a modest resistance to gemcitabine. The patients with a higher REG4 level, but not carcinoembryonic antigen or CA-19-9, showed an unfavorable histologic response to chemoradiotherapy (Spearman, rho = 0.439, P = 0.039). The patients showing a higher REG4 level experienced local recurrence postoperatively.Conclusions: These data demonstrated in vitro and in vivo that REG4 protein overexpression was associated with an unfavorable response to preoperative chemoradiotherapy. REG4 can clinically be used as a predictive biomarker.