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循环肿瘤干细胞预测肝癌肝切除术后复发:一项前瞻性研究。

Prediction of posthepatectomy recurrence of hepatocellular carcinoma by circulating cancer stem cells: a prospective study.

机构信息

State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong, China.

出版信息

Ann Surg. 2011 Oct;254(4):569-76. doi: 10.1097/SLA.0b013e3182300a1d.

DOI:10.1097/SLA.0b013e3182300a1d
PMID:21892074
Abstract

OBJECTIVE

To investigate whether circulating cancer stem cells (CSCs) of hepatocellular carcinoma (HCC) can predict its recurrence after hepatectomy.

BACKGROUND

HCC recurrence frequently occurs within the first year after hepatectomy, probably due to circulating tumor cells that have been shed from the primary tumor before hepatectomy. Because CSCs are more likely to initiate tumor growth than mature cancer cells, a high level of circulating CSCs may be a hint for HCC recurrence.

METHODS

Multicolor flow cytometry was used to detect the number of circulating CSCs (CD45CD90CD44) in the peripheral circulation of 82 HCC patients 1 day before hepatectomy. The patients were monitored by CT or MRI for recurrence every 3 months.

RESULTS

Forty-one (50%) patients had recurrence after a median follow-up period of 13.2 months (range, 1.3-57.1 months). Patients with recurrence had a higher median level of circulating CSCs than patients without recurrence (0.02% vs. 0.01%; P < 0.0001). Circulating CSCs > 0.01% predicted intrahepatic recurrence (relative risk 3.54; 95% CI, 1.41-8.88; P = 0.007) and extrahepatic recurrence (relative risk 10.15; 95% CI, 3-34.4; P = 0.0002). Patients with >0.01% circulating CSCs had a lower 2-year recurrence-free survival rate (22.7% vs. 64.2%; P < 0.0001) and overall survival rate (58.5% vs. 94.1%; P = 0.0005) than patients with ≤0.01% circulating CSCs. On multivariable analysis, circulating CSCs > 0.01%, tumor stage and tumor size were independent factors predicting recurrence-free survival.

CONCLUSIONS

Circulating CSCs predicted posthepatectomy HCC recurrence with high accuracy. They may be the target of eradication in the prevention of posthepatectomy HCC metastasis and recurrence.

摘要

目的

研究肝癌(HCC)患者的循环肿瘤干细胞(CSC)是否可以预测肝癌切除术后的复发。

背景

肝癌切除术后的 1 年内常发生复发,这可能是由于在切除前肿瘤已脱落的循环肿瘤细胞。由于 CSC 比成熟癌细胞更有可能引发肿瘤生长,因此高水平的循环 CSC 可能是 HCC 复发的提示。

方法

使用多色流式细胞术检测 82 例 HCC 患者在肝切除术前 1 天外周血中循环 CSC(CD45CD90CD44)的数量。通过 CT 或 MRI 对所有患者每 3 个月进行 1 次复发监测。

结果

中位随访 13.2 个月(范围,1.3-57.1 个月)后,41 例(50%)患者复发。与未复发患者相比,复发患者的循环 CSC 中位数水平更高(0.02% vs. 0.01%;P < 0.0001)。循环 CSC > 0.01%可预测肝内复发(相对风险 3.54;95%CI,1.41-8.88;P = 0.007)和肝外复发(相对风险 10.15;95%CI,3-34.4;P = 0.0002)。循环 CSC > 0.01%的患者 2 年无复发生存率(22.7% vs. 64.2%;P < 0.0001)和总生存率(58.5% vs. 94.1%;P = 0.0005)均低于循环 CSC ≤ 0.01%的患者。多变量分析显示,循环 CSC > 0.01%、肿瘤分期和肿瘤大小是无复发生存的独立预测因素。

结论

循环 CSC 可准确预测 HCC 切除术后的复发,可能是预防 HCC 切除术后转移和复发的治疗靶点。

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