The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma

Cell Communication and Signaling

Shimiao Cheng¹  Liyun Zheng¹  Kai Fan²  Bufu Tang²  Jinyu Zhu²  Jie Li²  Fazong Wu³  Jiansong Ji³  Yang Gao³  Chunli Kong³  Qiaoyou Weng³  Chenying Lu³ 

[1] Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, 323000, Lishui, China;Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, 323000, Lishui, China;Department of Radiology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 310058, Hangzhou, China;Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, Lishui Hospital, School of Medicine, Zhejiang University, 323000, Lishui, China;Department of Radiology, the Fifth Affiliated Hospital of Wenzhou Medical University, 323000, Lishui, China;

关键词: Ferroptosis;    Hepatocellular carcinoma (HCC);    TMB;    Immune microenvironment;    Prognosis;   

DOI  :  10.1186/s12964-020-00663-1

来源: Springer

【 摘 要 】

BackgroundIn this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC.MethodsIntegrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes.ResultsFour genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy.ConclusionsThe prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients.6i5hPu8DcyHvJLmULV1p7nVideo AbstractGraphical abstract

【 授权许可】

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