Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Rd, Chongqing, 400016, China.
Chongqing Key Laboratory of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Hepatol Int. 2019 Sep;13(5):631-640. doi: 10.1007/s12072-019-09969-w. Epub 2019 Jul 24.
The diagnostic potential of hepatic stellate cells (HSCs) and γδT cells for patients with hepatocellular carcinoma (HCC) and their synergistic contributions to the prognosis of these patients have not yet been investigated. The aim of this study was to elucidate the prognostic value of these cells in HCC.
The prognostic significance of the ratio of HSCs to γδT cells (SGR) was assessed in a total of 339 HCC patients undergoing resection. The correlation between the circulating tumor cell (CTC) level and SGR in 71 HCC patients was determined using the CellSearch system. In vitro experiments were performed to validate the synergistic effects of HSCs and γδT cells on hepatoma cells.
Peritumoral SGR was closely associated with overall survival (OS) and recurrence-free survival (RFS) of HCC patients after resection. In the testing cohort, two nomograms incorporating the SGR were constructed for the prediction of OS and RFS. The predictive accuracy of the two nomograms was verified by the validation cohort. CTC levels were positively correlated with SGR (r = 0.479, p < 0.001). Among the patients with CTCs > 2/7.5 ml, those with a high SGR exhibited higher early recurrence rates than those with a low SGR. In vitro experiments revealed that the secretion of INF-γ, IL-17, and TNF-α from γδT cells was increased after culture with HSC-conditioned medium. In addition, γδT cells cultured with HSC-conditioned medium decreased the proliferative and invasive abilities of hepatoma cells.
The peritumoral SGR is related to aggressive tumor behavior and has a powerful predictive value in HCC. Early recurrence in patients with a high peritumoral SGR might be associated with high CTC levels.
尚未研究肝星状细胞（HSCs）和γδT 细胞对肝细胞癌（HCC）患者的诊断潜力及其对这些患者预后的协同作用。本研究旨在阐明这些细胞在 HCC 中的预后价值。
在总共 339 例接受切除术的 HCC 患者中评估了 HSCs 与 γδT 细胞（SGR）比值的预后意义。使用 CellSearch 系统确定了 71 例 HCC 患者循环肿瘤细胞（CTC）水平与 SGR 的相关性。进行了体外实验以验证 HSCs 和 γδT 细胞对肝癌细胞的协同作用。
肿瘤周围 SGR 与 HCC 患者切除术后的总生存期（OS）和无复发生存期（RFS）密切相关。在测试队列中，构建了两个包含 SGR 的列线图，用于预测 OS 和 RFS。验证队列验证了两个列线图的预测准确性。CTC 水平与 SGR 呈正相关（r=0.479，p<0.001）。在 CTCs>2/7.5 ml 的患者中，SGR 较高的患者比 SGR 较低的患者早期复发率更高。体外实验显示，HSC 条件培养基培养后 γδT 细胞分泌的 INF-γ、IL-17 和 TNF-α增加。此外，HSC 条件培养基培养的 γδT 细胞降低了肝癌细胞的增殖和侵袭能力。
肿瘤周围 SGR 与侵袭性肿瘤行为有关，在 HCC 中具有强大的预测价值。高肿瘤周围 SGR 患者的早期复发可能与高 CTC 水平有关。
