单位:[1]Shanxi Med Univ, Hosp 2, West Branch, Dept Resp Gastroenterol & Oncol, Taiyuan, Peoples R China[2]Shanxi Med Univ, Sch Publ Hlth, Div Hlth Stat, Taiyuan, Peoples R China[3]Shanxi Med Univ, Shanxi Acad Med Sci, Shanxi Bethune Hosp, Tongji Shanxi Hosp,Hosp 3,Dept Psychiat, Taiyuan, Peoples R China[4]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China华中科技大学同济医学院附属同济医院[5]Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA[6]Shanxi Med Univ, Yidu Cloud Inst Med Data Sci, Taiyuan, Peoples R China
Hepatocellular carcinoma (HCC) is a leading malignant liver tumor with high mortality and morbidity. Patients at the same stage can be defined as different molecular subtypes associated with specific genomic disorders and clinical features. Thus, identifying subtypes is essential to realize efficient treatment and improve survival outcomes of HCC patients. Here, we applied a regularized multiple kernel learning with locality preserving projections method to integrate mRNA, miRNA and DNA methylation data of HCC patients to identify subtypes. We identified two HCC subtypes significantly correlated with the overall survival. The patient 3-years mortality rates in the high-risk and low-risk group was 51.0% and 23.5%, respectively. The high-risk group HCC patients were 3.37 times higher in death risk compared to the low-risk group after adjusting for clinically relevant covariates. A total of 196 differentially expressed mRNAs, 2,151 differentially methylated genes and 58 differentially expressed miRNAs were identified between the two subtypes. Additionally, pathway activity analysis showed that the activities of six pathways between the two subtypes were significantly different. Immune cell infiltration analysis revealed that the abundance of nine immune cells differed significantly between the two subtypes. We further applied the weighted gene co-expression network analysis to identify gene modules that may affect patients prognosis. Among the identified modules, the key module genes significantly associated with prognosis were found to be involved in multiple biological processes and pathways, revealing the mechanism underlying the progression of HCC. Hub gene analysis showed that the expression levels of CDK1, CDCA8, TACC3, and NCAPG were significantly associated with HCC prognosis. Our findings may bring novel insights into the subtypes of HCC and promote the realization of precision medicine.
基金:
NSFC; Applied Basic Research Project of Shanxi Province [71403156, 8210053813]; Shanxi Medical University-Yidu Cloud Institute of Medical Data Science [201901D111204]; Startup Foundation for Doctors of Shanxi Medical University [IMDS/SXMU-2020]; [BS201722]
第一作者单位:[1]Shanxi Med Univ, Hosp 2, West Branch, Dept Resp Gastroenterol & Oncol, Taiyuan, Peoples R China
通讯作者:
通讯机构:[2]Shanxi Med Univ, Sch Publ Hlth, Div Hlth Stat, Taiyuan, Peoples R China[3]Shanxi Med Univ, Shanxi Acad Med Sci, Shanxi Bethune Hosp, Tongji Shanxi Hosp,Hosp 3,Dept Psychiat, Taiyuan, Peoples R China[4]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Wuhan, Peoples R China[6]Shanxi Med Univ, Yidu Cloud Inst Med Data Sci, Taiyuan, Peoples R China
推荐引用方式(GB/T 7714):
Wang Jiaying,Miao Yuting,Li Lingmei,et al.Multi-omics data integration for hepatocellular carcinoma subtyping with multi-kernel learning[J].FRONTIERS IN GENETICS.2022,13:doi:10.3389/fgene.2022.962870.
APA:
Wang, Jiaying,Miao, Yuting,Li, Lingmei,Wu, Yongqing,Ren, Yan...&Cao, Hongyan.(2022).Multi-omics data integration for hepatocellular carcinoma subtyping with multi-kernel learning.FRONTIERS IN GENETICS,13,
MLA:
Wang, Jiaying,et al."Multi-omics data integration for hepatocellular carcinoma subtyping with multi-kernel learning".FRONTIERS IN GENETICS 13.(2022)