Promoter aberrant methylation status of<i>ADRA1A</i>is associated with hepatocellular carcinoma

Chen, Guoqiao; Fan, Xiaohui; Li, Yirun; He, Liangmei; Wang, Shanjuan; Dai, Yili; Cui, Bin; Zhou, Dake; Lin, Hui

doi:10.1080/15592294.2019.1709267

Cited by 25 publications

(24 citation statements)

References 41 publications

(44 reference statements)

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“…Moreover, TOP2A has also been a valuable prognostic marker for tumor advancements, recurrences, and predictors of poor survival in a variety of cancers, such as breast, ovarian, colon, and small cell lung cancer ( 29 ). ADRA1A encodes the alpha-1 adrenergic receptor subtype with catecholamines ligands ( 31 ), which is located on chromosome 8p ( 32 ). ADRA1A can stimulate the sympathetic nervous system to compete with some functions ( 33 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma

Sun

Zhao³

et al. 2021

Front. Oncol.

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BackgroundThis study aimed to systematically investigate gene signatures for hepatoblastoma (HB) and identify potential biomarkers for its diagnosis and treatment.Materials and MethodsGSE131329 and GSE81928 were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between hepatoblastoma and normal samples were identified using the Limma package in R. Then, the similarity of network traits between two sets of genes was analyzed by weighted gene correlation network analysis (WGCNA). Cytoscape was used to visualize and select hub genes. PPI network of hub genes was construed by Cytoscape. GO enrichment and KEGG pathway analyses of hub genes were carried out using ClueGO. The random forest classifier was constructed based on the hub genes using the GSE131329 dataset as the training set, and its reliability was validated using the GSE81928 dataset. The resulting core hub genes were combined with the InnateDB database to identify the innate core genes.ResultsA total of 4244 DEGs in HB were identified. WGCNA identified four modules that were significantly correlated with the disease status. A total of 114 hub genes were obtained within the top 20 genes of each node rank. 6982 relation pairs and 3700 nodes were contained in the PPI network of 114 hub genes. GO enrichment and KEGG pathway analyses of hub genes were focused on MAPK, cell cycle, p53, and other crucial pathways involved in HB. A random forest classifier was constructed using the 114 hub genes as feature genes, resulting in a 95.5% true positive rate when classifying HB and normal samples. A total of 35 core hub genes were obtained through the mean decrease in accuracy and mean decrease Gini of the random forest model. The classification efficiency of the random forest model was 81.4%. Finally, CDK1, TOP2A, ADRA1A, FANCI, XRCC1, TPX2, CCNB2, CDK4, GLYATL1, and CFHR3 were identified by cross-comparison with the InnateDB database.ConclusionOur study established a random forest classifier that identified 10 core genes in HB. These findings may be beneficial for the diagnosis, prediction, and targeted therapy of HB.

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Section: Discussionmentioning

confidence: 99%

Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma

Sun

Zhao³

et al. 2021

Front. Oncol.

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“…Cancer develops through the accumulation of genetic and epigenetic aberrations, and epigenetic changes are strongly associated with the development of HCC. As reported, many genes such as ADRAIA, ACADS, UBE2Q1, and ZCCH13 have been found to have aberrant methylation status in HCC (Hu et al 2017;Chen et al 2019;Li et al 2019;Chen et al 2020). Abnormal methylation of genes may be promising biomarkers to timely and accurately distinguish patients with HBV-associated HCC from patients with CHB.…”

Section: Discussionmentioning

confidence: 83%

Diagnostic Value of the Hypomethylation of the <i>WISP1</i> Promoter in Patients with Hepatocellular Carcinoma Associated with Hepatitis B Virus

Chen

Lin

Sun

et al. 2020

Tohoku J. Exp. Med.

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Wnt1-inducible signaling pathway protein 1 (WISP1) regulates cell proliferation, differentiation, adhesion, migration and survival. Abnormal WISP1 expression is associated with the carcinogenesis of hepatocellular carcinoma (HCC). Aberrant DNA methylation is one of the major epigenetic alterations in HCC. However, the methylation status of the WISP1 promoter is still unclear. We therefore aimed to determine the methylation status of the WISP1 promoter and evaluate its clinical value in HCC. The study enrolled 251 participants, including 123 participants with HCC, 90 participants with chronic hepatitis B (CHB) and 38 healthy controls (HCs). WISP1 methylation status, mRNA levels and plasma soluble WISP1 were detected by methylation-specific polymerase chain reaction (MSP), quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. We found that the methylation frequency of WISP1 in patients with HCC was significantly lower than that in patients with CHB and HCs, while the relative expression levels of WISP1 mRNA were markedly higher in patients with HCC than in patients with CHB and HCs. Furthermore, the plasma soluble WISP1 in patients with HCC was obviously lower than in that in patients with CHB and HCs. Alpha-fetoprotein (AFP) is a widely recognized biomarker to diagnose HCC which lacks enough sensitivity and specificity. WISP1 promoter methylation status combined with AFP significantly improved the diagnostic ability in discriminating HCC from CHB compared with AFP or WISP1 methylation status alone. In conclusion, hypomethylation of the WISP1 gene promoter may serve as a noninvasive biomarker for detecting HBV-associated HCC.

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“…Like the results in this study, the level of methylation at different sites has very different effects on the prognosis of patients. In recent years, studies have shown that methylation of the RIZ1 gene promoter region in HCC tissues is associated with postoperative tumor recurrence, which may be the reason for the poor prognosis of patients with RIZ1 gene methylation positive in HCC tissues ( 21 ); Similarly, another study also showed that Compared with normal tissues, the methylation level of the ADRA1A promoter region in the tumor tissues of HCC patients was significantly increased, the mRNA and protein levels of ADRA1A were decreased, and DNA methyltransferase inhibitors could increase the mRNA expression of ADRA1A ( 22 ). It shows that ADRA1A gene hypermethylation may be involved in the occurrence of HCC.…”

Section: Discussionmentioning

confidence: 98%

ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma

et al. 2022

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Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and effective targets for treating HCC patients are in the spotlight of HCC therapy. Zinc Finger CCHC-Type Containing 17 (ZCCHC17) encodes the RNA binding protein ZCCHC17, but its role in HCC is still unclear. Here, 90 paraffin-embedded specimens combined with bioinformatics were used to comprehensively clarify the value of ZCCHC17 in the diagnosis and prognosis of HCC and its potential functions. Paraffin-embedded specimens were used to assess ZCCHC17 protein expression and its correlation with prognosis in 90 HCC patients. the public data sets of HCC patients from TCGA, ICG, and GEO databases were also used for further analysis. It was found that protein and mRNA levels of ZCCHC17 in HCC tissues were significantly higher than those in normal tissues. The abnormally high expression may be related to the abnormal DNA methylation of ZCCHC17 in tumor tissues. The high expression of ZCCHC17 is related to AFP, histologic grade, tumor status, vascular invasion, and pathological stage. Multi-data set analysis showed that patients with high ZCCHC17 expression had a worse prognosis, and multivariate cox regression analysis showed an independent prognostic significance of ZCCHC17. The results of functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), indicate that ZCCHC17 is mainly involved in immune regulation. Subsequently, further single-sample gene set enrichment analysis (ssGSEA) showed that the expression of ZCCHC17 was related to the infiltration of immune cells. Importantly, we also analyzed the relationship between ZCCHC17 and immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI) and TP53 status in HCC patients and evaluated the role of ZCCHC17 in cancer immunotherapy. In summary, ZCCHC17 is a novel marker for the diagnosis and prognostic evaluation of HCC. Concurrently, it regulates immune cells in the tumor microenvironment (TME) of HCC patients, which has a specific reference value for the immunotherapy of HCC.

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Promoter aberrant methylation status ofADRA1Ais associated with hepatocellular carcinoma

Cited by 25 publications

References 41 publications

Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma

Identification of Ten Core Hub Genes as Potential Biomarkers and Treatment Target for Hepatoblastoma

Diagnostic Value of the Hypomethylation of the <i>WISP1</i> Promoter in Patients with Hepatocellular Carcinoma Associated with Hepatitis B Virus

ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma

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