胃癌中循环肿瘤细胞及其核型特征与临床分期的相关性

Circulating tumor cells and their karyotyping correlates with pathological staging in gastric cancer

目的分析循环肿瘤细胞(CTC)在胃癌辅助诊断中的作用及其与胃癌临床病理特征的相关性,探讨其临床意义。方法纳入98例胃癌患者和38例胃部良性疾病患者,采用阴性富集联合免疫荧光原位杂交(imFISH)检测平台检测患者CTC,分析CTC及其核型特征与临床病理特征的关系。结果胃癌患者中CTC检出率(CTC≥1)为94.9%,而胃部良性疾病患者中CTC检出率为28.9%,两者差异显著(P<0.001)。ROC曲线显示,当cut-off值定为2个细胞/3.2ml血时,CTC在胃癌诊断中的灵敏度为89.8%,特异性为89.5%(AUC=0.945,95%CI, 0.908-0.982,P<0.001)。CTC在Ⅰ～Ⅱ期和Ⅲ～Ⅳ期胃癌患者中的检出率(CTC≥1)分别为84.6%和98%,在T1～T2和T3～T4期患者中CTC检出率分别为81.3%和96.7%,在N0、N1～N3患者中CTC检出率分别为81.3%和96.5%,在上述分组中检出率有显著差异(p<0.05)。在性别、年龄、肿瘤分化程度、Her2表达、Ki-67表达及M分期等分组中,CTC阳性率差异不显著。8号染色体多体CTC在Ⅲ～Ⅳ期患者中的阳性率为69.6%,显著高于Ⅰ～Ⅱ期患者(44%,P<0.05)。结论阴性富集联合imFISH技术在胃癌CTC检测中具有较高的灵敏度和特异性,对于胃癌的辅助诊断和早期检测具有重要意义。同时,CTC总数及8号染色体多体CTC与胃癌TNM分期密切相关,或可用于胃癌分期的辅助判断和预后评估。

Objective This study investigated the role of circulating tumor cells（CTCs） in the diagnosis of gastric cancer and the correlation of gastric cancer CTCs with the clinicopathological features. Methods CTCs in 98 gastric cancer patients and 38 nonmalignant gastric disease patients were detected by negative enrichment and immunofluorescence in situ hybridization platform. Correlation of gastric cancer CTCs and their karyotyping with clinicopathological features were analyzed. Results CTCs were detected in 28.9% nonmalignant gastric disease patients and 94.9% gastric cancer patients. The difference between gastric cancer patients and the control cohort was statistically significant（P〈0.001）. ROC curve demonstrated that when the cut-off value was 2 cells/3.2 ml, the sensitivity of CTCs in the diagnosis of gastric cancer was 89.80%, and the specificity was 89.47%（AUC=0.945, 95%CI, 0.908-0.982, P〈0.001）.And 84.6% of stage I-II and 98% of stage III-IV patients were found to have CTC≥1/3.2 ml（P〈0.05）. Furthermore, the incidence of CTCs was significantly different between the T1-T2（81.3%） and T3-T4（96.7%） groups（P〈0.05）, as well as lymph node metastasis positive（96.5%） and negative groups（81.3%, P〈0.05）.There was no significant difference in CTC positive rate between the groups of sex, age, tumor differentiation, tissue HER2 expression, tissue Ki-67 expression and M staging. Furthermore, the positive rate of multiploid chromosome 8 CTCs in patients with stage III-IV was 69.57%, which was significantly higher than that in patients with stageⅠ-Ⅱ（44%, P=0.037）. Conclusion By using negative enrichment and imFISH platform, the sensitivity and specificity in diagnosis of gastric cancer can be improved. At the same time, the CTC counts and multiploid chromosome 8 CTCs are closely related to the TNM staging. It is of potential clinical utility in terms of early diagnosis and predicting prognosis.