Bao-Yong Zhou1, Jun-Hua Gong2,3, Xiao-Yan Cai4, Jia-Xing Wang5, Fang Luo1, Ning Jiang6, Jian-Ping Gong2,3, Cheng-You Du1, Rui Liao7. 1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Rd, Chongqing, 400016, China. 2. Chongqing Key Laboratory of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. 3. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China. 4. Department of General Surgery, Gongli Hospital of Shanghai Pudong New Area, Shanghai, 200135, China. 5. Department of Anesthesiology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China. 6. Department of Pathology, Chongqing Medical University, Chongqing, 400016, China. 7. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yixueyuan Rd, Chongqing, 400016, China. liaorui99@163.com.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.