Multi-Omics Integrative Analysis Uncovers Molecular Subtypes and mRNAs as Therapeutic Targets for Liver Cancer

Frontiers in Medicine

article

Yi Shen¹  Wei Xiong¹  Qi Gu¹  Qin Zhang¹  Jia Yue¹  Changsong Liu¹  Duan Wang¹ 

[1] Department of Cardiovascular Medicine, The Third Affiliated Hospital of Chongqing Medical University

关键词: liver cancer;    multi-omics;    molecular subtype;    ANXA2;    CHAF1B;    mRNA;    therapeutic target;   

DOI  :  10.3389/fmed.2021.654635

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Objective: This study aimed to systematically analyze molecular subtypes and therapeutic targets of liver cancer using integrated multi-omics analysis. Methods: DNA copy number variations (CNVs), simple nucleotide variations (SNVs), methylation, transcriptome as well as corresponding clinical information for liver carcinoma were retrieved from The Cancer Genome Atlas (TCGA). Multi-omics analysis was performed to identify molecular subtypes of liver cancer via integrating CNV, methylation as well as transcriptome data. Immune scores of two molecular subtypes were estimated using tumor immune estimation resource (TIMER) tool. Key mRNAs were screened and prognosis analysis was performed, which were validated using RT-qPCR. Furthermore, mutation spectra were analyzed in the different subtypes. Results: Two molecular subtypes (iC1 and iC2) were conducted for liver cancer. Compared with the iC2 subtype, the iC1 subtype had a worse prognosis and a higher immune score. Two key mRNAs (ANXA2 and CHAF1B) were significantly related to liver cancer patients' prognosis, which were both up-regulated in liver cancer tissues in comparison to normal tissues. Seventeen genes with p < 0.01 differed significantly for SNV loci between iC1 and iC2 subtypes. Conclusion: Our integrated multi-omics analyses provided new insights into the molecular subtypes of liver cancer, helping to identify novel mRNAs as therapeutic targets and uncover the mechanisms of liver cancer.

【 授权许可】

CC BY