Evaluation of cytokeratin-19 mRNA as a tumor marker in the peripheral blood of nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy

Evaluation of cytokeratin-19 mRNA as a tumor marker in the peripheral blood of nasopharyngeal carcinoma patients receiving concurrent chemoradiotherapy
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DOI:
10.1002/ijc.10075
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发表时间:
2002-02-01
影响因子:
6.4
通讯作者:
Wei, YH
Wei, YH
中科院分区:
医学1区
文献类型:
--
作者:
Lin, JC;Chen, KY;Wei, YH

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逆转录-聚合酶链反应(RTPCR)技术是一种能够检测微量循环肿瘤细胞衍生转录本的工具。鼻咽癌(Nasopharyngealcarcinoma,NPC)是一种生长迅速的上皮性肿瘤,具有高度转移潜能.本研究旨在探讨鼻咽癌患者循环细胞角蛋白19(CK-19)mRNA检测的临床价值。1997年6月至1999年3月,57例未经治疗的晚期NPC患者接受同步放化疗。治疗前前瞻性采集外周血样本,并进行巢式RT-PCR检测。采取措施防止污染和假基因干扰。阳性结果的PCR产物经限制性内切酶Hae II和直接测序验证。在我们的巢式RT-PCR实验条件下,33.3%(19/57)的临床非转移性NPC患者的血液中有CK-19 mRNA。不同分期患者外周血CK-19 mRNA的阳性检出率分别为II期20.0%、III期31.6%、IV期43.5%(p=0.1335)。中位随访时间为35个月后,2例患者的原发肿瘤复发,14例发生远处转移,无局部复发。9/19例(47.4%)CK-19 mRNA阳性患者和5/38例(13.2%)CK-19 mRNA阴性患者发生远处转移(p=0.00826)。CK-19可检测患者的3年无转移生存率为49.9%,CK-19不可检测患者为85.9%(p=0.0089,对数秩检验)。提示外周血CK-19 mRNA的表达可能是鼻咽癌微转移的一个潜在标志。(C)2002 Wiley-Liss,Inc.
The reverse transcriptase-polymerase chain reaction (RTPCR) technique is a tool capable of detecting minute quantities of circulating tumor cell-derived transcripts. Nasopharyngeal carcinoma (NPC) is a rapidly growing tumor of epithelial origin and high metastatic potential. The aim of our study is to investigate the clinical value of circulating cytokeratin-19 (CK-19) mRNA detection in NPC patients. Between June 1997 and March 1999, 57 previously untreated, advanced NPC patients without distant metastasis were uniformly treated by concurrent chemoradiotherapy. Peripheral blood samples were collected prospectively before treatment and subjected to a nested RT-PCR assay. Measures were taken to prevent contamination and pseudogene interference. PCR products of positive results were verified by restriction enzyme Hae II and direct sequencing. Under our nested RT-PCR experimental conditions, 33.3% (19/57) clinically nonmetastatic NPC patients had CK-19 mRNA in their blood. The positive detection rates of CK-19 mRNA in the peripheral blood for different stages were 20.0% for stage II, 31.6% stage III and 43.5% stage IV (p=0.1335). After a median follow-up time of 35 months, 2 patients had recurrences of their primary tumors and 14 developed distant metastases without locoregional recurrence. Nine of 19 (47.4%) CK-19 mRNA-positive patients and 5 of 38 (13.2%) CK-19 mRNA-negative patients developed distant metastasis (p=0.00826). The 3-year metastasis-free survival rates were 49.9% for patients with detectable CK-19 and 85.9% for those with undetectable CK-19 (p=0.0089, log-rank test). Our data suggest that the presence of CK-19 mRNA in the peripheral blood may be a potential marker of micrometastasis for NPC. (C) 2002 Wiley-Liss, Inc.