Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China.
J Gastrointest Surg. 2018 Apr;22(4):633-639. doi: 10.1007/s11605-017-3619-3. Epub 2017 Nov 20.
Circulating tumor cells (CTCs) have been actively studied for their functions in hepatocellular carcinoma (HCC) recurrence. However, the relationship between circulating tumor cells subtypes and hepatocellular carcinoma recurrence is still unclear.
CTCs were collected from the peripheral blood of 62 postoperative HCC patients. The CTCs were isolated with a filtration-based method. Multiplex fluorescence in situ hybridization was used to characterize the CTCs based on mRNA expression levels of epithelial and mesenchymal markers.
Of the 62 HCC patients, 26 were diagnosed with early recurrence (ER) and 36 did not experience recurrence. Comparison between the recurrence group and the non-recurrence group showed the total number of CTCs, mesenchymal CTCs, and mixed CTCs in the recurrence group was significantly higher than in the non-recurrence group. Receiver operator characteristic (ROC) curve analysis was performed to define the positive cutoff values as follows: total number of CTCs ≥ 4, mesenchymal CTCs ≥ 1, and mixed CTCs ≥ 3. Analysis showed that portal vein tumor thrombus (hazard ratio [HR] = 2.905, P = 0.023) and mesenchymal CTC positivity (HR = 3.453, P = 0.007) were independent risk factors for ER. The correlation between the presence of mesenchymal CTCs and time to recurrence was further examined, and the results showed significantly shortened postoperative disease-free survival in patients positive for mesenchymal CTCs (P < 0.001).
HCC patients with positive peripheral mesenchymal CTCs have a more serious risk of ER, which could be a potential biomarker in HCC prognosis monitoring.
循环肿瘤细胞（CTC）在肝癌（HCC）复发中的作用已被广泛研究。然而，循环肿瘤细胞亚型与肝癌复发之间的关系仍不清楚。
从 62 例术后 HCC 患者的外周血中采集 CTCs。采用基于过滤的方法分离 CTCs。采用多重荧光原位杂交技术，根据上皮和间充质标志物的 mRNA 表达水平对 CTCs 进行特征分析。
在 62 例 HCC 患者中，26 例被诊断为早期复发（ER），36 例未复发。复发组与非复发组比较，复发组总 CTCs、间充质 CTCs 和混合 CTCs 数量明显高于非复发组。进行Receiver operator characteristic（ROC）曲线分析，定义阳性截断值如下：总 CTCs≥4、间充质 CTCs≥1、混合 CTCs≥3。分析表明门静脉癌栓（HR=2.905，P=0.023）和间充质 CTC 阳性（HR=3.453，P=0.007）是 ER 的独立危险因素。进一步分析了间充质 CTC 阳性与复发时间的相关性，结果显示间充质 CTC 阳性患者术后无病生存率明显缩短（P<0.001）。
外周血间充质 CTC 阳性的 HCC 患者复发风险更高，可能成为 HCC 预后监测的潜在生物标志物。
