Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Monday, 03 / 08 / 2021

Articles

ORIGINAL ARTICLE

A Deep Look into the Program of Rapid Tumor Growth of Hepatocellular Carcinoma

Jie Wang†,1,2, Yi Lou†,3 , Jianmin Lu4Yuxiao Luo4Anqian Lu1Anna Chen1Jiantao Fu1Jing Liu1,2Xiang Zhou*,1,2 and Jin Yang*,1,2

1  Department of Translational Medicine, Affiliated Hospital of Hangzhou Normal University, Institute of Hepatology and Metabolic Diseases of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China
2  Department of Liver Disease, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China
3  Department of Occupational Medicine, Hangzhou Red Cross Hospital, Zhejiang Provincial Integrated Chinese and Western Medicine Hospital, Hangzhou, Zhejiang, China
4  Department of Orthopedics, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China
†  These authors contributed equally to this work.
*Correspondence to: Jin Yang, Department of Translational Medicine, Affiliated Hospital of Hangzhou Normal University, Institute of Hepatology and Metabolic Diseases of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China. Tel: +86-571-88358062, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ; Xiang Zhou, Department of Liver Disease, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang 310015, China. Tel: +86-571-88303403, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Journal of Clinical and Translational Hepatology 2021;9(1):22-31 DOI: 10.14218/JCTH.2020.00084
Received: September 7, 2020 AcceptedDecember 1, 2020 Published online: January 4, 2021

Abstract

Background and Aims: Great efforts have been made towards increasing our understanding of the pathogenesis involved in hepatocellular carcinoma (HCC), but the rapid growth inherent to such tumor development remains to be explored.

Methods: We identified distinct gene coexpression modes upon liver tumor growth using weighted gene coexpression network analysis. Modeling of tumor growth as signaling activity was employed to understand the main cascades responsible for the growth. Hub genes in the modules were determined, examined in vitro, and further assembled into the growth signature.

Results: We revealed modules related to the different growth states in HCC, especially the fastest growth module, which is preserved among different HCC cohorts. Moreover, signaling flux in the cell cycle pathway was found to act as a driving force for rapid growth. Twenty hub genes in the module were identified and assembled into the growth signature, and two genes (NCAPH, and RAD54L) were tested for their growth potential in vitro. Genetic alteration of the growth signature affected the global gene expression. The activity of the signature was associated with tumor metabolism and immunity in HCC. Finally, the prognosis effect of the growth signature was reproduced in nine cancers.

Conclusions: These results collectively demonstrate the molecule organization of rapid tumor growth in HCC, which is a highly synergistic process, with implications for the future management of patients.

Keywords

Hepatocellular carcinoma, Tumor growth, Coexpression network, Cell cycle, Metabolism

Journal of Clinical and Translational Hepatology 2021 vol. 9, 22-31  [ Html  ] [ PDF Full-text ]

© The Author(s) 2021. This article is published under the terms of the Creative Commons Attribution-Noncommercial License (CC BY-NC 4.0), which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

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