Hypoxia-based classification and prognostic signature for clinical management of hepatocellular carcinoma
-
Published:2023-07-22
Issue:1
Volume:21
Page:
-
ISSN:1477-7819
-
Container-title:World Journal of Surgical Oncology
-
language:en
-
Short-container-title:World J Surg Onc
Author:
Li Ke,Yang Yanfang,Ma Mingwei,Lu Suping,Li Junjie
Abstract
Abstract
Objective
Intratumoral hypoxia is an essential feature of hepatocellular carcinoma (HCC). Herein, we investigated the hypoxia-based heterogeneity and relevant clinical implication in HCC.
Methods
Three HCC cohorts: TCGA-LIHC, LICA-FR, and LIRI-JP were retrospectively gathered. Consensus clustering analysis was utilized for hypoxia-based classification based upon transcriptome of hypoxia genes. Through LASSO algorithm, a hypoxia-relevant prognostic signature was built. Immunotherapeutic response was inferred through analyzing immune checkpoints, T cell inflamed score, TIDE score, and TMB score. RNF145 expression was measured in normoxic or hypoxic HCC cells. In RNF145-knockout cells, CCK-8, TUNEL, and scratch tests were implemented.
Results
HCC patients were classified into two hypoxia subtypes, with more advanced stages and poorer prognosis in cluster2 than cluster1. The heterogeneity in tumor infiltrating immune cells and genetic mutation was found between subtypes. The hypoxia-relevant prognostic model was proposed, composed of ANLN, CBX2, DLGAP5, FBLN2, FTCD, HMOX1, IGLV1-44, IL33, LCAT, LPCAT1, MKI67, PFN2, RNF145, S100A9, and SPP1). It was predicted that high-risk patients presented worse prognosis with an independent and reliable manner. Based upon high expression of immune checkpoints (CD209, CTLA4, HAVCR2, SIRPA, TNFRSF18, TNFRSF4, and TNFRSF9), high T cell inflamed score, low TIDE score and high TMB score, high-risk patients might respond to immunotherapy. Experimental validation showed that RNF145 was upregulated in hypoxic HCC cells, RNF145 knockdown attenuated proliferation and migration, but aggravated apoptosis in HCC cells.
Conclusion
Altogether, the hypoxia-based classification and prognostic signature might be useful for prognostication and guiding treatment of HCC.
Publisher
Springer Science and Business Media LLC
Reference43 articles.
1. Johnson P, Zhou Q, Dao DY, Lo YMD. Circulating biomarkers in the diagnosis and management of hepatocellular carcinoma. Nat Rev Gastroenterol Hepatol. 2022;19:670–81. 2. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894–905. 3. Mazzaferro V, Citterio D, Bhoori S, Bongini M, Miceli R, de Carlis L, Colledan M, Salizzoni M, Romagnoli R, Antonelli B, Vivarelli M, Tisone G, Rossi M, Gruttadauria S, di Sandro S, de Carlis R, Lucà MG, de Giorgio M, Mirabella S, Belli L, Fagiuoli S, Martini S, Iavarone M, SvegliatiBaroni G, Angelico M, GinanniCorradini S, Volpes R, Mariani L, Regalia E, Flores M, Drozdibusset M, Sposito C. Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial. Lancet Oncol. 2020;21:947–56. 4. Zhang MS, Cui JD, Lee D, Yuen VW, Chiu DK, Goh CC, Cheu JW, Tse AP, Bao MH, Wong BPY, Chen CY, Wong CM, Ng IO, Wong CC. Hypoxia-induced macropinocytosis represents a metabolic route for liver cancer. Nat Commun. 2022;13:954. 5. Salman S, Meyers DJ, Wicks EE, Lee SN, Datan E, Thomas AM, Anders NM, Hwang Y, Lyu Y, Yang Y, Jackson W 3rd, Dordai D, Rudek MA, Semenza GL. HIF inhibitor 32–134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy. J Clin Invest. 2022;132:e156774.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|