Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection
Relationship between pancreatic secretory trypsin inhibitor and early recurrence of intrahepatic cholangiocarcinoma following surgical resection
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DOI：
10.1111/j.1572-0241.2006.00612.x
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发表时间：
2006-07-01
影响因子：
9.8
通讯作者：
Miyazaki, Masaru
中科院分区：
文献类型：
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作者：
Tonouchi, Akihiko;Ohtsuka, Masayuki;Miyazaki, Masaru
目的：肝内胆管细胞癌（ICC）的预后极差，即使在手术切除后，主要是由于高复发率。本研究的目的是确定与早期复发的ICC以下surgence.METHODS：1984年12月至2003年7月，46例ICC患者进行了手术切除的分子。根据复发时间评价这些患者的临床结局。因此，我们根据临床结果将ICC患者分为亚组，并通过DNA微阵列分析筛选差异表达基因。此外，所获得的结果进行了验证，在一个独立的样本集，通过定量实时逆转录聚合酶链反应（RT-PCR）。免疫组化法在蛋白水平上检测基因表达。与术后1年以上复发的患者相比，术后1年内早期复发的患者术后甚至复发后的生存率显著降低。通过DNA微阵列分析，筛选出13个差异表达基因，定量RT-PCR检测胰腺分泌型胰蛋白酶抑制剂（PSTI）基因表达，结果显示PSTI基因可能是ICC术后早期复发的候选基因。通过对一组独立样本的检查证实了这一观察结果，其中PSTI mRNA表达水平较高的患者无复发生存期明显较短。免疫组化显示PSTI在癌细胞胞浆中表达。结论：PSTI可能是一个潜在的标志物，用于识别ICC患者手术切除后早期复发的风险增加。
OBJECTIVES: The extremely unfavorable prognosis of intrahepatic cholangiocarcinoma (ICC), even after surgical resection, is mainly attributed to a high rate of recurrence. The aim of this study was to identify the molecules associated with early recurrence of ICC following resection.METHODS: Between December 1984 and July 2003, 46 patients with ICC underwent surgical resection. The clinical outcome of these patients was evaluated in view of the time of recurrence. Consequently, we categorized ICC patients into subgroups, based on the clinical results, and screened differentially expressed genes by DNA microarray analysis. Furthermore, the obtained results were validated in an independent sample set by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemistry was performed to assess the expressed genes at the protein level.RESULTS: The survival of patients with early recurrence, occurring within a year after surgical resection, was significantly poor after surgery and even after recurrence, as compared to that of patients whose recurrence occurred beyond a year after surgery.By the DNA microarray analysis, 13 differentially expressed genes were picked up, and quantitative RT-PCR reaction identified the pancreatic secretory trypsin inhibitor (PSTI) as a candidate gene associated with early recurrence of ICC after resection. This observation was confirmed through examination of an independent set of samples, in which the patients with higher levels of PSTI mRNA expression had significantly shorter recurrence-free survival. Immunohistochemically, PSTI was expressed in the cytoplasm of cancer cells.CONCLUSIONS: PSTI might be a potential marker for identifying ICC patients with an increased risk of early recurrence after surgical resection.