Dong Guoping, Fan Fangying, He Yao, Luo Yanchun, Yu Jie, Liang Ping
Department of Interventional Ultrasound, Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
Chinese PLA Medical School, Beijing, 100853, People's Republic of China.
J Hepatocell Carcinoma. 2023 Aug 2;10:1267-1279. doi: 10.2147/JHC.S420836. eCollection 2023.
Extrahepatic metastasis in hepatocellular carcinoma (HCC) greatly limits the prognostic survival of HCC patients. Levels of preoperative peripheral lymphocyte subsets and cytokines in the serum for predicting extrahepatic spread of hepatocellular carcinoma are still not common in clinical practice. The aim of this study is to investigate the value and mechanisms of peripheral lymphocyte subsets and cytokines in predicting extrahepatic spread of HCC.
We used a retrospective design to analyze data pertaining to a total of 380 patients with HCC who were examined for peripheral T-lymphocyte subsets before receiving microwave ablation. We performed Cox regression analysis to screen out independent risk factors and used pathology specimens from the patients and public databases of liver cancer to investigate the correlation between cytokines and intra-tumor immune cells.
The CD4 group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD4 group (80% vs 69%, 67% vs 51%, and 57% vs 39%, respectively; HR 1.7 (1.2, 2.3), P = 0.0019). Similarly, the CD8 group had better metastasis-free 1-year, 3-year, and 5-year survival rates compared to the CD8 group (65% vs 78%, 46% vs 64%, and 34% vs 54%, respectively; HR 0.6 (0.4, 0.8), P < 0.001). Patients with the CD4/CD8 phenotype had significantly worse metastasis-free survival times compared to other patients (HR 2.0 (1.5, 2.8), P < 0.001). Additionally, T lymphocyte-specific genes (CD4, CD8) were correlated with CCL5 expression, which was also positively correlated with the level of intra-tumoral infiltrating CD8 T cells and the prognosis of HCC patients.
Both CD4 and CD8 T lymphocyte subsets were independent risk factors for extrahepatic metastasis in HCC. Serum CCL5 levels could indicate the infiltration level of intra-tumoral CD8 T cells and the risk of extrahepatic metastasis in HCC patients, aiding in patient risk stratification for metastasis.
肝细胞癌（HCC）的肝外转移极大地限制了HCC患者的预后生存。术前外周血淋巴细胞亚群水平和血清细胞因子用于预测肝细胞癌肝外转移在临床实践中仍不常见。本研究旨在探讨外周血淋巴细胞亚群和细胞因子在预测HCC肝外转移中的价值及机制。
我们采用回顾性设计，分析了380例HCC患者在接受微波消融术前检测外周血T淋巴细胞亚群的数据。我们进行Cox回归分析以筛选出独立危险因素，并利用患者的病理标本和肝癌公共数据库研究细胞因子与肿瘤内免疫细胞之间的相关性。
与CD4组相比，CD4组的1年、3年和5年无转移生存率更高（分别为80%对69%、67%对51%、57%对39%；HR 1.7（1.2，2.3），P = 0.0019）。同样，与CD8组相比，CD8组的1年、3年和5年无转移生存率更高（分别为65%对78%、46%对64%、34%对54%；HR 0.6（0.4，0.8），P < 0.001）。与其他患者相比，具有CD4/CD8表型的患者无转移生存时间明显更差（HR 2.0（1.5，2.8），P < 0.001）。此外，T淋巴细胞特异性基因（CD4、CD8）与CCL5表达相关，CCL5表达也与肿瘤内浸润性CD8 T细胞水平及HCC患者预后呈正相关。
CD4和CD8 T淋巴细胞亚群均为HCC肝外转移的独立危险因素。血清CCL5水平可指示肿瘤内CD8 T细胞浸润水平及HCC患者肝外转移风险，有助于对转移患者进行风险分层。
