Abstract
Liver cancer is a lethal disease that is associated with poor prognosis. In order to identify the functionally important genes associated with liver cancer that may reveal novel therapeutic avenues, we performed integrated analysis to profile miRNA and mRNA expression levels for liver tumors compared to normal samples in The Cancer Genome Atlas (TCGA) database. We identified 405 differentially expressed genes and 233 differentially expressed miRNAs in tumor samples compared with controls. In addition, we also performed the pathway analysis and found that mitogen-activated protein kinases (MAPKs) and G-protein coupled receptor (GPCR) pathway were two of the top significant pathway nodes dysregulated in liver cancer. Furthermore, by examining these signaling networks, we discovered that FOS (Fos proto-oncogene, AP-1 transcription factor subunit), LAMC2 (laminin subunit gamma 2), and CALML3 (calmodulin like 3) were the most significant gene nodes with high degrees involved in liver cancer. The expression and disease prediction accuracy of FOS, LAMC2, CALML3, and their interacting miRNAs were further performed using a HCC cohort. Finally, we investigated the prognostic significance of FOS in another HCC cohort. Patients with higher FOS expression displayed significantly shorter time to recurrence (TTR) and overall survival (OS) compared with patients with lower expression. Collectively, our study demonstrates that FOS is a potential prognostic marker for liver cancer that may reveal a novel therapeutic avenue in this lethal disease.
Highlights
Liver cancer is a lethal disease often caused by liver damage associated with virus infection, excessive alcohol, or other liver disease [1]
The studies of cancer genetics and genomic sequencing have contributed to deeper understanding of the underlying cause of liver cancer [4]. e gene expression profiling analysis has improved the classification of liver cancer subtypes [5]. e discovery of mutations in BRAF (B-Raf proto-oncogene, a serine/threonine kinase) and EGFR by DNA sequencing contributed to the development of new targeted therapies for liver cancer patients carrying these mutations
Risk Genes for Liver Cancer Analysis. e targets of experiment-validated differentially expressed (DE) miRNAs were predicted based on miRecords, miRTarBase, and TarBase. e target genes were mapped to DE mRNAs, and the overlapped genes were defined as the risk genes of liver cancer
Summary
Liver cancer is a lethal disease often caused by liver damage associated with virus infection, excessive alcohol, or other liver disease [1]. It ranks the sixth most common cancer worldwide and accounts for the fourth most common cause of cancer related death due to lack of effective therapies [2]. MiR-122 was found to be expressed at lower levels in liver cancer cells compared to normal hepatocytes by gene expression profiling, contributing to its function on liver cancer cell migration and invasion [10]. The molecule marker for liver cancer has not been fully investigated
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