Abstract
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.
Highlights
Liver cancer is the fifth largest malignant tumor and the second leading cause of cancer-related deaths worldwide [1, 2]
As depicted in the distribution of CNVCor genes on chromosomes, CNVCor genes most frequently occurred on chr1 (FDR
The box plots showed the distribution in pearson correlation coefficients of CNVCor genes on chromosomes (Figure 1B). 16037 methylation sites corresponding 6181 genes were identified under the screening criteria of p < 0.01 (Supplementary Table 2)
Summary
Liver cancer is the fifth largest malignant tumor and the second leading cause of cancer-related deaths worldwide [1, 2]. The mortality of liver cancer accounts for about 6% of death cases of cancers in men and 3% of death cases in women [3]. Several potential risk factors contribute to the occurrence and development of liver cancer, including chronic hepatitis B/C virus infection, alcoholism and aflatoxin exposure [4]. Under the exposure of these risk factors, genetics and epigenetic changes may be gradually accumulated, thereby leading to activation of oncogenes and inactivation of tumor suppressor genes, which in turn will lead to the occurrence of liver cancer [5, 6]
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