Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma.

Autor:	Li B; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.; Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA., Li Y; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Zhou H; Department of Data Science & Bioinformatics, Crown Bioscience Inc., Suzhou, Jiangsu, China., Xu Y; Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China., Cao Y; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Cheng C; Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Affiliated Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, China., Peng J; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Li H; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Zhang L; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Su K; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Xu Z; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Hu Y; Biobank of Nanjing Drum Tower Hospital, Department of Pathology, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Nanjing, China., Lu J; Department of Radiology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China., Lu Y; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Qian L; Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, China., Wang Y; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Zhang Y; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Liu Q; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Xie Y; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China., Guo S; Department of Data Science & Bioinformatics, Crown Bioscience Inc., Suzhou, Jiangsu, China., Mehal WZ; Department of Internal Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut, USA., Yu D; State Key Laboratory of Pharmaceutical Biotechnology, Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.; Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China.; Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Affiliated Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing, China.
Jazyk:	angličtina
Zdroj:	Hepatology (Baltimore, Md.) [Hepatology] 2024 Feb 01; Vol. 79 (2), pp. 289-306. Date of Electronic Publication: 2023 Aug 07.
DOI:	10.1097/HEP.0000000000000553
Abstrakt:	Background and Aims: Molecular classification is a promising tool for prognosis prediction and optimizing precision therapy for HCC. Here, we aimed to develop a molecular classification of HCC based on the fatty acid degradation (FAD) pathway, fully characterize it, and evaluate its ability in guiding personalized therapy. Approach and Results: We performed RNA sequencing (RNA-seq), PCR-array, lipidomics, metabolomics, and proteomics analysis of 41 patients with HCC, in which 17 patients received anti-programmed cell death-1 (PD-1) therapy. Single-cell RNA sequencing (scRNA-seq) was performed to explore the tumor microenvironment. Nearly, 60 publicly available multiomics data sets were analyzed. The associations between FAD subtypes and response to sorafenib, transarterial chemoembolization (TACE), immune checkpoint inhibitor (ICI) were assessed in patient cohorts, patient-derived xenograft (PDX), and spontaneous mouse model ls. A novel molecular classification named F subtype (F1, F2, and F3) was identified based on the FAD pathway, distinguished by clinical, mutational, epigenetic, metabolic, and immunological characteristics. F1 subtypes exhibited high infiltration with immunosuppressive microenvironment. Subtype-specific therapeutic strategies were identified, in which F1 subtypes with the lowest FAD activities represent responders to compounds YM-155 and Alisertib, sorafenib, anti-PD1, anti-PD-L1, and atezolizumab plus bevacizumab (T + A) treatment, while F3 subtypes with the highest FAD activities are responders to TACE. F2 subtypes, the intermediate status between F1 and F3, are potential responders to T + A combinations. We provide preliminary evidence that the FAD subtypes can be diagnosed based on liquid biopsies. Conclusions: We identified 3 FAD subtypes with unique clinical and biological characteristics, which could optimize individual cancer patient therapy and help clinical decision-making. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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