胃癌患者外周血癌胚抗原mRNA表达及其临床意义分析

The Expression of Carcinoembryonic Antigen mRNA in the Peripheral Blood of Gastric Cancer Patients and Its Clinical Significance

目的:探讨胃癌患者外周血癌胚抗原(CEA)mRNA表达及其与相关病理因素、近期疗效、预后的关系。方法:应用TaqMan定量逆转录-聚合酶链反应(RT-PCR)检测58例胃癌患者化疗前、后20例健康对照者外周血癌胚抗原CEA mRNA表达;同时采用化学发光法测定胃癌患者血清CEA水平。患者随访2年。结果:胃癌患者外周血CEAmRNA阳性率为56.89%(33/58),显著高于健康对照组,二者差异有统计学意义(P<0.001);胃癌患者外周血CEAmRNA表达与肿瘤浸润深度(P=0.035)、淋巴结转移(P=0.042)、远处转移(P=0.006)和血清CEA水平相关(P=0.001);多因素Logistic回归分析表明:淋巴结转移和血清CEA水平是影响胃癌患者外周血CEA mRNA表达的独立因素;血清CEA阳性率31.03%(18/58),胃癌患者外周血CEA mRNA的阳性率显著高于CEA蛋白水平(χ2=7.873,P=0.005),TaqMan定量RT-PCR与化学发光法检测CEA的符合率为88.89%(化学发光法检测阳性的病例TaqMan定量RT-PCR检测阳性率);化疗后CEA mRNA阳性率略有下降,但不显著。近期疗效无效的患者外周血CEA mRNA的阳性率显著高于近期疗效有效的患者(χ2=9.992,P=0.002)。平均随访2年后,CEA mRNA阳性患者与阴性患者的1年生存率分别是33.33%和77.27%,差异具有显著性(P=0.002)。结论:外周血CEA mRNA可作为检测胃癌患者肿瘤细胞微转移的分子标志;定期监测胃癌患者外周血CEA mRNA表达有助于评估化疗疗效和预测预后。肿瘤浸润深度和血清CEA蛋白水平与外周血肿瘤细胞微转移相关。CEA mRNA的检测优于蛋白水平的检测,有助于胃癌的早期诊断。

Objective： To investigate the expression of carcinoembryonic antigen （CEA） mRNA in the peripheral blood of patients with gastric cancer and its correlation with pathological factors, chemotherapy response and prognosis. Methods： The expression of CEA mRNA in peripheral blood was detected with TaqMan reverse transcriptase-polymerase chain reaction （RT-PCR） in 58 patients with gastric cancer before and after chemotherapy and in 20 healthy subjects. Serum CEA protein levels were also measured by chemiluminescent immunoassay before treatment. The patients were followed up for 2 years. Results： The positive rate of CEA mRNA in patients with gastric cancer was 56.9% （33/58）, significantly higher than in the healthy controls （P〈0.001）. Univariate analysis revealed that the depth of tumor invasion （P=0.035）, lymphatic metastasis （P=0.042）, distant metastasis （P=0.006） and serum CEA protein levels （P=0.001） were related to the CEA mRNA expression in peripheral blood. Multivariate logistic regression showed that lymphatic metastasis and serum CEA protein levels were independent factors for CEA mRNA expression. The positive rate of CEA mRNA was higher than that of serum CEA protein. The detection rates of chemiluminescent immunoassay and TaqMan RT-PCR for CEA were consistent （88.9%）. The positive rate of CEA mRNA did not decrease significantly after 2 cycles of chemotherapy （P〉0. 05）, but the positive rate of CEA mRNA in patients with no response to chemotherapy was significantly higher than that in patients who responded. The 1-year survival rate in patients with detectable CEA mRNA before chemotherapy was lower than that in patients with no detectable CEA mRNA, and the difference between the two groups was significant （P=0. 002）. Conclusion： CEA mRNA can be used as a marker in the detection of tumor micrometastasis in gastric cancer patients, and regular quantification of CEA mRNA in peripheral blood may be important in evaluating chemotherapy response and prognosis. Lymphatic metastasis and serum CEA protein levels appeared to be highly correlated with gastric cancer hematogenous metastasis. Expression of CEA mRNA is a better marker than serum CEA protein expression and therefore may be useful for eady diagnosis of gastric cancer.