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胰腺癌患者循环肿瘤细胞的标志物表达。

Marker expression in circulating cancer cells of pancreatic cancer patients.

机构信息

Department of Hepatic-Biliary Surgery, Affiliated Zhongda Hospital, Southeast University, Nanjing, China.

出版信息

J Surg Res. 2011 Dec;171(2):631-6. doi: 10.1016/j.jss.2010.05.007. Epub 2010 Jun 1.

DOI:10.1016/j.jss.2010.05.007
PMID:20869080
Abstract

BACKGROUND

By the time patients are diagnosed with pancreatic cancer, circulating cancer cells probably exist. Therefore, the detection of pancreatic cancer cells in the peripheral circulation could be used to diagnose early pancreatic cancer, which would otherwise not be detected by current imaging methods.

METHODS

The expression levels of h-TERT, CK20, CEA, and C-MET were detected in a model of circulating micrometastasis in pancreatic cancer that were enriched using immune-magnetic separation of the circulating cancer cells. The sensitivity and specificity of the measurements were evaluated. The expression of the above genes was measured in the circulating cancer cells of pancreatic cancer patients. We compared their expression rate in pancreatic cancer patients at different stages to screen for the indicator with highest sensitivity and specificity for the detection of circulating pancreatic cancer cells.

RESULTS

Immuno-magnetic nanoparticles combined with RT-PCR enabled the detection of one tumor cell per 1×10(7) peripheral blood mononuclear cells. The positive expression rates of C-MET, h-TERT, CK20, and CEA in the pancreatic cancer group were 80% (20/25), 100% (25/25), 84% (21/25), and 80% (20/25), respectively, while in the benign disease control group the rates were 0% (0/15), 0% (0/15), 6.77% (1/15), and 0% (0/15), respectively. There was a significant difference in the positive expression rate between the two groups (P<0.05). The specificity of h-TERT, CEA, and C-MET was higher than that of CK20. The positive expression rate of the four genes was not related to gender, age, tumor size, CA 19-9, or CEA serum levels (P>0.05). However, the positive expression of C-MET, CK20, and CEA closely correlated with tumor stage (P<0.05). Immuno-magnetic nanoparticles combined with RT-PCR were specific and sensitive for the detection of circulating cancer cells.

CONCLUSIONS

The positive expression of C-MET, h-TERT, CK20, and CEA in the circulation of pancreatic patients could be used as an indicator for circulating cancer cells. The combined detection of the four genes improved the specificity and sensitivity to 100%, which may be attributable to the use of immuno-magnetic separation and enrichment of the circulating pancreatic cancer cells. Our results suggest the clinical utility of this approach.

摘要

背景

当患者被诊断出患有胰腺癌时,循环中的癌细胞可能已经存在。因此,检测外周循环中的胰腺癌细胞可用于诊断早期胰腺癌,而目前的成像方法可能无法检测到这种癌症。

方法

使用免疫磁珠分离法富集胰腺癌循环微转移模型中的循环癌细胞,检测其中 h-TERT、CK20、CEA 和 C-MET 的表达水平。评估测量的灵敏度和特异性。测量胰腺癌患者循环癌细胞中上述基因的表达情况,比较不同分期胰腺癌患者的表达率,筛选出对检测循环胰腺癌细胞具有最高灵敏度和特异性的指标。

结果

免疫磁珠联合 RT-PCR 可检测到每 1×10(7)个外周血单个核细胞中有 1 个肿瘤细胞。胰腺癌组中 C-MET、h-TERT、CK20 和 CEA 的阳性表达率分别为 80%(20/25)、100%(25/25)、84%(21/25)和 80%(20/25),而良性疾病对照组的阳性表达率分别为 0%(0/15)、0%(0/15)、6.77%(1/15)和 0%(0/15),两组比较差异有统计学意义(P<0.05)。h-TERT、CEA 和 C-MET 的特异性高于 CK20。这四种基因的阳性表达与性别、年龄、肿瘤大小、CA 19-9 或 CEA 血清水平无关(P>0.05)。然而,C-MET、CK20 和 CEA 的阳性表达与肿瘤分期密切相关(P<0.05)。免疫磁珠联合 RT-PCR 对循环癌细胞的检测具有特异性和敏感性。

结论

胰腺癌患者循环中 C-MET、h-TERT、CK20 和 CEA 的阳性表达可作为循环癌细胞的标志物。四种基因联合检测的特异性和敏感性提高到 100%,这可能归因于免疫磁珠分离和富集循环胰腺癌细胞。我们的结果表明了这种方法的临床应用价值。

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