Author:
Yang Jiabin,Zeng Liangtang,Chen Ruiwan,Zheng Shangyou,Zhou Yu,Chen Rufu
Abstract
BackgroundMetabolic reprogramming is a well-known hallmark of cancer. Systematical identification of clinically relevant metabolic subtypes of Hepatocellular carcinoma (HCC) is critical to understand tumor heterogeneity and develop efficient treatment strategies.MethodsWe performed an integrative analysis of genomic, transcriptomic, and clinical data from an HCC patient cohort in The Cancer Genome Atlas (TCGA).ResultsFour metabolic subtypes were defined: mHCC1, mHHC2, mHCC3, and mHCC4. These subtypes had distinct differences in mutations profiles, activities of metabolic pathways, prognostic metabolism genes, and immune features. The mHCC1 was associated with poorest outcome and was characterized by extensive metabolic alterations, abundant immune infiltration, and increased expression of immunosuppressive checkpoints. The mHHC2 displayed lowest metabolic alteration level and was associated with most significant improvement in overall survival in response to high CD8+ T cell infiltration. The mHHC3 was a “cold-tumor” with low immune infiltration and few metabolic alterations. The mHCC4 presented a medium degree of metabolic alteration and high CTNNB1 mutation rate. Based on our HCC classification and in vitro study, we identified palmitoyl-protein thioesterase 1 (PPT1) was a specific prognostic gene and therapeutic target for mHCC1.ConclusionOur study highlighted mechanistic differences among metabolic subtypes and identified potential therapeutic targets for subtype-specific treatment strategies targeting unique metabolic vulnerabilities. The immune heterogeneities across metabolic subtypes may help further clarify the association between metabolism and immune environment and guide the development of novel strategies through targeting both unique metabolic vulnerabilities and immunosuppressive triggers.
Subject
Immunology,Immunology and Allergy
Reference66 articles.
1. Cancer statistics, 2022;Siegel;CA Cancer J Clin,2022
2. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma;Maluccio;CA Cancer J Clin,2012
3. Sorafenib in advanced hepatocellular carcinoma;Llovet;N Engl J Med,2008
4. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (Resorce): A randomised, double-blind, placebo-controlled, phase 3 trial;Bruix;Lancet,2017
5. Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: Multicentre, open-label, phase ii safety study;Bruix;Eur J Cancer (Oxford Engl 1990),2013
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