Yang Modan, Lin Zuyuan, Zhuang Li, Pan Linhui, Wang Rui, Chen Hao, Hu Zhihang, Shen Wei, Zhuo Jianyong, Yang Xinyu, Li Huigang, He Chiyu, Yang Zhe, Xie Qinfen, Dong Siyi, Chen Junli, Su Renyi, Wei Xuyong, Yin Junjie, Zheng Shusen, Lu Di, Xu Xiao
Department of Breast Surgery The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou China.
NHC Key Laboratory of Combined Multi-Organ Transplantation Zhejiang University Hangzhou China.
MedComm (2020). 2024 Aug 26;5(9):e678. doi: 10.1002/mco2.678. eCollection 2024 Sep.
Tumor recurrence is a life-threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation-related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety-three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha-fetoprotein, systemic immune-inflammation index, interleukin 6, and osteocalcin in the training cohort ( = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C-index: 0.736). The high IFP group recipients had significantly worse 3-year recurrence-free survival rates (37.9 vs. 86.9%, < 0.001). Simultaneous T-cell profiling revealed that recipients with high IFP were characterized by impaired T cell function. The IFP also performed well in the validation cohort ( = 103, AUROC: 0.807, C-index: 0.681). In conclusion, the IFP efficiently predicted posttransplant HCC recurrence and helped to refine pretransplant risk stratification. Impaired T cell function might be the intrinsic mechanism for the high recurrence risk of recipients in the high IFP group.
肿瘤复发是肝细胞癌（HCC）肝移植（LT）后危及生命的并发症。移植前精确的复发风险分层对于受者的管理至关重要。在此，我们旨在基于移植前外周细胞因子谱建立一种与炎症相关的肝移植后HCC复发预测模型。纳入了在两个独立医疗中心接受LT的293例患者，并将他们移植前的血浆样本送去进行细胞因子谱分析。通过COX回归分析，我们在训练队列（n = 190）中确定了四个独立危险因素，包括甲胎蛋白、全身免疫炎症指数、白细胞介素6和骨钙素。基于上述因素建立了一个名为炎症指纹（IFP）的预测模型。IFP有效地预测了移植后复发（受试者操作特征曲线下面积[AUROC]：0.792，C指数：0.736）。高IFP组受者的3年无复发生存率显著更差（37.9%对86.9%，P < 0.001）。同时进行的T细胞谱分析显示，高IFP受者的特征是T细胞功能受损。IFP在验证队列（n = 103，AUROC：0.807，C指数：0.681）中也表现良好。总之，IFP有效地预测了肝移植后HCC复发，并有助于完善移植前风险分层。T细胞功能受损可能是高IFP组受者高复发风险的内在机制。
