International Journal of General Medicine (Dec 2021)
Liquid–Liquid Phase Separation-Related Genes Associated with Tumor Grade and Prognosis in Hepatocellular Carcinoma: A Bioinformatic Study
Abstract
Zhao-Shan Fang,1,* Zhi Zhang,1,* Zhi-Jie Liang,2 Zhong-Rong Long,1 Yi Xiao,1 Zhi-Yin Liang,1 Xing Sun,1 Hong-Mian Li,3 Hai Huang4 1Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 2Department of Wound Repair Surgery, The Fifth Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530022, People’s Republic of China; 3Department of Medical Laboratory Center, The Fifth Affiliated Hospital of Guangxi Medical University, Guangxi, 530022, People’s Republic of China; 4Department of Hepatobiliary Surgery, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Mian LiDepartment of Medical Laboratory Center, The Fifth Affiliated Hospital of Guangxi Medical University, Guangxi, 530022, People’s Republic of ChinaEmail [email protected] HuangDepartment of Hepatobiliary Surgery, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of ChinaEmail [email protected]: The aim of the present study was to identify the association between tumor grade and liquid–liquid phase separation (LLPS)-related genes, and to generate a LLPS-related gene-based risk index (LLPSRI) as a prognostic tool for hepatocellular carcinoma (HCC).Methods: Weighted gene correlation network analysis was performed to test whether the LLPS-related gene modules were associated with tumor grade of HCC. The candidate modules were subjected to functional enrichment analysis. We generated a LLPSRI using the expression profiles of the hub genes among the candidate modules in order to identify patients at high risk. Then, the biological characteristics of the high-risk patients were revealed using gene set enrichment analysis. Additionally, an independent external data set was used to validate the LLPSRI.Results: Four gene modules showed a significant positive correlation with tumor grade and involved various cancer-related pathways. Among the hub genes, six were selected to generate the LLPSRI, which was significantly associated with prognosis of HCC patients. The LLPSRI could successfully divide patients with HCC into high- and low-risk groups, and patients in the high-risk group showed shorter overall survival than those in the low-risk group. E2F, MYC, and mTORC1 signaling may be important determinants of survival in the high-risk group. The prognostic value of the LLPSRI was validated with the independent external data set.Conclusion: We identified LLPS-related gene modules that are associated with HCC tumor grade. The LLPSRI may be useful as a prognostic marker of HCC, and it may reliably stratify patients into groups at low or high risk of worse survival. Our analysis also suggests that certain biological characteristics of HCC may be associated with high risk of worse survival.Keywords: hepatocellular carcinoma, liquid–liquid phase separation, WGCNA, prognostic biomarker
