解剖性肝切除的肝细胞癌患者门静脉循环肿瘤细胞的临床意义

Clinical Significance of Circulating Tumor Cells in the Portal Vein of Patients with Hepatocellular Carcinoma Undergoing Anatomical Liver Resection.

作者信息

Takei Daisuke, Kobayashi Tsuyoshi, Hamaoka Michinori, Matsubara Keiso, Oshita Ko, Namba Yosuke, Tadokoro Takeshi, Tanaka Yuka, Kuroda Shintaro, Ohdan Hideki

机构信息

Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

Department of Gastroenterological Surgery, National Hospital Organization, Shikoku Cancer Center, Matsuyama, Japan.

出版信息

Ann Surg Oncol. 2025 Sep 9. doi: 10.1245/s10434-025-18295-5.

DOI:10.1245/s10434-025-18295-5

PMID:40924249

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) frequently invades the portal vein, leading to early recurrence and a poor prognosis. However, the mechanisms underlying this invasion remain unclear. In this study, we aimed to detect portal vein circulating tumor cells (CTCs) using a Glypican-3-positive detection method and evaluate their prognostic significance.

METHODS

This prospective study included 146 patients with HCC who underwent open anatomical hepatectomy. Blood samples from the peripheral, portal, and hepatic veins were collected intraoperatively, and CTCs were detected using magnetic enrichment and flow cytometry. Programmed cell death ligand 1 (PD-L1) expression in portal CTCs was evaluated in 40 patients.

RESULTS

Portal vein CTCs were detected in 45.8% of cases, more frequently than hepatic vein CTCs (p = 0.031). Portal vein CTC positivity correlated with microscopic portal vein invasion (p < 0.001), poorer disease-free survival (p = 0.014), and overall survival (p = 0.001). PD-L1-positive portal vein CTCs were observed in 13 of 40 cases (32.5%) and were significantly associated with poorer prognosis (p = 0.001).

CONCLUSIONS

Portal vein CTCs are significant predictors of portal vein invasion, recurrence, and survival in HCC. PD-L1-positive portal vein CTCs may contribute to immune evasion and tumor progression. These findings suggest that portal vein CTCs are valuable prognostic biomarkers and potential therapeutic targets.

摘要

背景

肝细胞癌（HCC）常侵犯门静脉，导致早期复发和预后不良。然而，这种侵袭的潜在机制仍不清楚。在本研究中，我们旨在使用磷脂酰肌醇蛋白聚糖-3阳性检测方法检测门静脉循环肿瘤细胞（CTC），并评估其预后意义。

方法

这项前瞻性研究纳入了146例行开放性解剖性肝切除术的HCC患者。术中采集外周静脉、门静脉和肝静脉血样，采用磁性富集和流式细胞术检测CTC。对40例患者评估门静脉CTC中程序性细胞死亡配体1（PD-L1）的表达。

结果

45.8%的病例检测到门静脉CTC，其检出率高于肝静脉CTC（p = 0.031）。门静脉CTC阳性与门静脉微小侵犯相关（p < 0.001），无病生存期较差（p = 0.014），总生存期较差（p = 0.001）。40例中有13例（32.5%）观察到PD-L1阳性门静脉CTC，且与较差的预后显著相关（p = 0.001）。