Abstract

Considering the high fatality of hepatocellular carcinoma (HCC), current prognostic systems are insufficient to accurately forecast HCC patients' outcomes. In our study, nine anoikis‑related genes (PTRH2, ITGAV, ANXA5, BIRC5, BDNF, BSG, DAP3, SKP2, and EGF) were determined to establish a risk scoring model using LASSO regression, which could be validated in ICGC dataset. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curve analysis confirmed the risk score possessed an accurate predictive value for the prognosis of HCC patients. The high-risk group showed a higher infiltration of aDCs, macrophages, T-follicular helper cells, and Th2 cells. Besides, PD-L1 was significantly higher in the high-risk group compared to the low-risk group. Several anoikis‑related genes, such as ANX5, ITGAV, BDNF and SKP2, were associated with drug sensitivity in HCC. Finally, we identified BIRC5 and SKP2 as hub genes among the nine model genes using WGCNA analysis. BIRC5 and SKP2 were over-expressed in HCC tissues, and their over-expression was associated with poor prognosis, no matter in our cohort by immunohistochemical staining or in the TCGA cohort by mRNA-Seq. In our cohort, BIRC5 expression was highly associated with the T stage, pathologic stage, histologic grade and AFP of HCC patients. In general, our anoikis-related risk model can enhance the ability to predict the survival outcomes of HCC patients and provide a feasible therapeutic strategy for immunotherapy and drug resistance in HCC. BIRC5 and SKP2 are hub genes of anoikis‑related genes in HCC.

Details

Title
Development of a prognostic model for anoikis and identifies hub genes in hepatocellular carcinoma
Author
Zhong, Zhiwei 1 ; Xie, Fuchun 2 ; Yin, Jiajun 3 ; Zhao, Hua 4 ; Zhou, Yuehan 4 ; Guo, Kun 5 ; Li, Rongkuan 1 ; Wang, Qimin 5 ; Tang, Bo 4 

 The Second Affiliated Hospital of Dalian Medical University, Department of Infectious Disease, Dalian, People’s Republic of China (GRID:grid.452828.1) (ISNI:0000 0004 7649 7439) 
 Guangdong Academy of Medical Sciences, Department of Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China (GRID:grid.410643.4) 
 Affiliated Zhongshan Hospital of Dalian University, Department of General Surgery, Dalian, People’s Republic of China (GRID:grid.459353.d) (ISNI:0000 0004 1800 3285) 
 The Second Affiliated Hospital of Dalian Medical University, Department of Hematology, Dalian, People’s Republic of China (GRID:grid.452828.1) (ISNI:0000 0004 7649 7439) 
 The Second Affiliated Hospital of Dalian Medical University, Department of Pathology, Dalian, People’s Republic of China (GRID:grid.452828.1) (ISNI:0000 0004 7649 7439) 
Pages
14723
Publication year
2023
Publication date
2023
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2861997536
Copyright
© Springer Nature Limited 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.