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

• Published in: Journal of clinical and translational hepatology Vol. 9; no. 1; pp. 22 - 10
• Main Authors: Wang, Jie, Lou, Yi, Lu, Jianmin, Luo, Yuxiao, Lu, Anqian, Chen, Anna, Fu, Jiantao, Liu, Jing, Zhou, Xiang, Yang, Jin
• Format: Journal Article
• Language: English
• Published: China Department of Translational Medicine, Affiliated Hospital of Hangzhou Normal University, Institute of Hepatology and Meta-bolic Diseases of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China 28-02-2021; Department of Liver Disease, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China%Department of Occupational Medicine, Hangzhou Red Cross Hospital, Zhejiang Provincial Integrated Chinese and Western Medicine Hospital, Hangzhou, Zhejiang, China%Department of Orthopedics, Affiliated Hospital of Hangzhou NormalUniversity, Hangzhou Normal University, Hangzhou, Zhejiang, China%Department of Translational Medicine, Affiliated Hospital of Hangzhou Normal University, Institute of Hepatology and Meta-bolic Diseases of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, China; XIA & HE Publishing Inc
• Subjects: Original; Hepatocellular carcinoma; Tumor growth; Metabolism; Cell cycle; Coexpression network
• ISSN: 2225-0719; 2310-8819
• DOI: 10.14218/JCTH.2020.00084

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.
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
, and further assembled into the growth signature.
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 (
, and
) were tested for their growth potential
. 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.
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.