Journal of Hepatocellular Carcinoma (Mar 2021)

Development and Validation of a Metabolic Gene-Based Prognostic Signature for Hepatocellular Carcinoma

  • Weng J,
  • Zhou C,
  • Zhou Q,
  • Chen W,
  • Yin Y,
  • Atyah M,
  • Dong Q,
  • Shi Y,
  • Ren N

Journal volume & issue
Vol. Volume 8
pp. 193 – 209

Abstract

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Jialei Weng,1,* Chenhao Zhou,1,2,* Qiang Zhou,1 Wanyong Chen,1,3 Yirui Yin,1 Manar Atyah,1 Qiongzhu Dong,2– 4 Yi Shi,5 Ning Ren1,3 1Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, People’s Republic of China; 2Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Institute of Fudan Minhang Academic Health System, Minhang Hospital, Key Laboratory of Shanghai Municipal Health Commission, Fudan University, Shanghai, People’s Republic of China; 4Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China; 5Biomedical Research Centre, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning RenDepartment of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of ChinaTel +86-21-64041990Email [email protected] ShiBiomedical Research Centre, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of ChinaTel +86-21-64041990Email [email protected]: Hepatocellular carcinoma (HCC) is a malignant tumor with great variation in prognosis among individuals. Changes in metabolism influence disease progression and clinical outcomes. The objective of this study was to determine the overall survival (OS) risk of HCC patients from a metabolic perspective.Patients and Methods: The model was constructed using the least absolute shrinkage and selection operator (LASSO) COX regression based on The Cancer Genome Atlas (TCGA, n=342) dataset. The International Cancer Genome Consortium (ICGC, n=232), GSE14520 (n=242) datasets, and a clinical cohort (n=64) were then used to assess the prognostic value of the signature.Results: A 10 metabolic gene-based signature was constructed and verified as a robust and independent prognostic classifier in public and real-world validation cohorts. Meanwhile, the signature enabled the identification of HCC molecular subtypes, yielding an AUC value of 0.678 [95% CI: 0.592– 0.763]. Besides, the signature was associated with metabolic processes like glycolysis, supported by a clear correlation between the risk score and expression of rate-limiting enzymes. Furthermore, high-risk tumor was likely to have a high tumor infiltration status of immunosuppressive cells, as well as elevated expression of some immune checkpoint molecules. For final clinical translation, a nomogram integrating the signature and tumor stage was established, and showed improved predictive accuracy of 3- and 5-year OS and brought more net benefit to patients.Conclusion: We developed a prognostic signature based on 10 metabolic genes, which has proven to be an independent and reliable prognostic predictor for HCC and reflects the metabolic and immune characteristics of tumors.Keywords: hepatocellular carcinoma, metabolism-related gene, signature, prognosis

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