首页|A Prognostic Nomogram for Hepatocellular Carcinoma Based on Wound Healing and Immune Checkpoint Genes

A Prognostic Nomogram for Hepatocellular Carcinoma Based on Wound Healing and Immune Checkpoint Genes

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Background and Aims: Wound healing and tumor progres-sion share some common biological features; however, how variations in wound healing patterns affect hepatocellular carcinoma (HCC) prognosis remains unclear. Methods: We analyzed the wound healing patterns of 594 HCC samples from The Cancer Genome Atlas (TCGA) and the Internation-al Cancer Genome Consortium (ICGC) and correlated them with immune infiltration and the expression levels of immune checkpoint genes. A risk score, which we named the "heal. immune" score, was established via stepwise Cox estima-tion. We constructed a nomogram based on age, sex, TNM stage, and heal.immune score and explored its predictive value for HCC prognosis. Seventy-four clinical patients were enrolled in this study, and all were from Huashan Hospital of Fudan University between 2015 and 2017 to serve as an in-dependent validation group. Results: We identified two dis-tinct wound healing patterns in HCC. The biological processes of healing cluster 1 (C1) are related to metabolism, while those of healing cluster 2 (C2) are related to the inflamma-tory response and immune cell accumulation. A total of 565 wound healing-related genes (based on Gene Ontology) and 25 immune checkpoint genes were considered. By analyz-ing differentially expressed genes and implementing a step-wise Cox estimation analysis, six genes with p values less than 0.02 in a multivariate Cox estimation were chosen as the "heal.immune" gene set (FCER1G, PLAT, ITGA5, CCNB1, CD86 and CD40). The "heal.immune" gene set, as an OS risk factor, was further validated in Fudan cohort. We constructed a nomogram to predict the 1-, 3- and 5-year overall survival (OS) in the TCGA cohort. The area under curve vales of the receiver characteristic operator curves were 0.82, 0.76 and 0.73 in the training group and 0.84, 0.76 and 0.72 in the test group. Conclusions: We established a prognostic nomogram based on the heal.immune gene signature, which includes six wound healing- and immunity-related genes. This nomogram accurately predicts the OS of HCC patients.

Hepatocellular carcinomaBioinformaticsImmune checkpointWound healingPrognosis

Beiyuan Hu、Xiaotian Shen、Wei Qin、Lan Zhang、Tiantian Zou、Qiongzhu Dong、Lun-Xiu Qin

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Department of General Surgery,Huashan Hospital&Cancer Metastasis Institute,Institutes of Biomedical Sciences,Fudan University,Shanghai,China

Program of Shanghai Aca-demic Research Leader国家自然科学基金国家自然科学基金国家自然科学基金中国博士后科学基金Project of Medical Engineering,Fudan Universitythe"Fuqing Scholar"Student Scientific Research Program of Shanghai Medical Col-lege

20XD14009008194007481772563816728202017M611459yg2021-017FQXZ202115B

2022

10.14218/JCTH.2021.00296

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

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年,卷(期)：2022.10(5)
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