An inflammatory liquid fingerprint predicting tumor recurrence after liver transplantation for hepatocellular carcinoma

Modan Yang; Zuyuan Lin; Li Zhuang; Linhui Pan; Rui Wang; Hao Chen; Zhihang Hu; Wei Shen; Jianyong Zhuo; Xinyu Yang; Huigang Li; Chiyu He; Zhe Yang; Qinfen Xie; Siyi Dong; Junli Chen; Renyi Su; Xuyong Wei; Junjie Yin; Shusen Zheng; Di Lu; Xiao Xu

doi:10.1002/mco2.678

MedComm ›› 2024, Vol. 5 ›› Issue (9) : e678 DOI: 10.1002/mco2.678

ORIGINAL ARTICLE

An inflammatory liquid fingerprint predicting tumor recurrence after liver transplantation for hepatocellular carcinoma

Modan Yang ¹^,²
, Zuyuan Lin ³^,⁴
, Li Zhuang ⁵
, Linhui Pan ⁶
, Rui Wang ⁴
, Hao Chen ⁴
, Zhihang Hu ⁴
, Wei Shen ⁴
, Jianyong Zhuo ⁶
, Xinyu Yang ³^,⁴
, Huigang Li ⁴
, Chiyu He ⁴
, Zhe Yang ⁵
, Qinfen Xie ⁵
, Siyi Dong ⁷
, Junli Chen ⁷
, Renyi Su ⁴
, Xuyong Wei ³^,⁶
, Junjie Yin ⁶
, Shusen Zheng ²^,⁵^,⁷^,^†
, Di Lu ⁸^,^†
, Xiao Xu ⁸^,⁹^,^†

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¹. Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

². NHC Key Laboratory of Combined Multi-Organ Transplantation, Zhejiang University, Hangzhou, China

³. Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, China

⁴. Zhejiang University School of Medicine, Hangzhou, China

⁵. Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, China

⁶. Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, China

⁷. National Center for Healthcare Quality Management in Liver Transplant, Hangzhou, China

⁸. Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), School of Clinical Medicine, Hangzhou Medical College, Hangzhou, China

⁹. Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China

shusenzheng@zju.edu.cn

zjuludi@zju.edu.cn

zjxu@zju.edu.cn

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Abstract

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 (n = 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%, p < 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 (n = 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.

Keywords

cytokines / hepatocellular carcinoma / liver transplantation / prognostic model / T-cell profiling

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Modan Yang, Zuyuan Lin, Li Zhuang, Linhui Pan, Rui Wang, Hao Chen, Zhihang Hu, Wei Shen, Jianyong Zhuo, Xinyu Yang, Huigang Li, Chiyu He, Zhe Yang, Qinfen Xie, Siyi Dong, Junli Chen, Renyi Su, Xuyong Wei, Junjie Yin, Shusen Zheng, Di Lu, Xiao Xu. An inflammatory liquid fingerprint predicting tumor recurrence after liver transplantation for hepatocellular carcinoma. MedComm, 2024, 5(9): e678 DOI:10.1002/mco2.678

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