The Clinical Value And Potential Molecular Mechanism Of The Downregulation Of Maoa In Hepatocellular Carcinoma Tissues

CANCER MEDICINE(2020)

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摘要
Background Hepatocellular carcinoma (HCC) remains one of the most common cancers worldwide and tends to be detected at an advanced stage. More effective biomarkers for HCC screening and prognosis assessment are needed and the mechanisms of HCC require further exploration. The role ofMAOAin HCC has not been intensively investigated. Methods In-house tissue microarrays, genechips, and RNAsequencing datasets were integrated to explore the expression status and the clinical value ofMAOAin HCC. Immunohistochemical staining was utilized to determine MAOA protein expression. Intersection genes ofMAOArelated co-expressed genes and differentially expressed genes were obtained to perform functional enrichment analyses. In vivo experiment was conducted to study the impact of traditional Chinese medicine nitidine chloride (NC) onMAOAin HCC. Results MAOAwas downregulated and possessed an excellent discriminatory capability in HCC patients. DecreasedMAOAcorrelated with poor prognosis in HCC patients. Downregulated MAOA protein was relevant to an advanced TNM stage in HCC patients. Co-expressed genes that positively related toMAOAwere clustered in chemical carcinogenesis, where CYP2E1 was identified as the hub gene. In vivo experiment showed that nitidine chloride significantly upregulatedMAOAin a nude mouse HCC model. Conclusions A decreasedMAOAlevel is not only correlated with aggressive behaviors in males but also serves as a promising biomarker for the diagnosis and prognosis of HCC patients. Moreover,MAOAmay play a role in AFB1 toxic transformation through its synergistic action with co-expressed genes, especially CYP3A4.MAOAalso serves as a potential therapy target of NC in HCC patients.
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关键词
gene chip, HCC, immunohistochemical staining, MAOA, RNA-seq, tissue microarray
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