<i>MT1M</i>and<i>MT1G</i>promoter methylation as biomarkers for hepatocellular carcinoma

Ji, Xiang‐Fen; Fan, Yu–Chen; Gao, Shuai; Yang, Yang; Zhang, Jianjun; Wang, Kai

doi:10.3748/wjg.v20.i16.4723

Cited by 65 publications

(54 citation statements)

References 32 publications

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“…Among these 33 publications, 11 articles described the diagnostic role of circulating Ras association domain family 1 isoform A ( RASSF1A ) methylation in HCC and eight articles evaluated the diagnostic performance of ctDNA combined with AFP assay in HCC . Nine articles assessed the diagnostic accuracy of AFP assay for HCC …”

Section: Resultsmentioning

confidence: 99%

Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

et al. 2019

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Purpose A meta‐analysis was formulated to appraise the diagnostic accuracy of circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC). Materials and Methods We enrolled all relevant studies published until September 2019. Four primary subgroups were investigated: the subgroup of quantitative or qualitative analysis of ctDNA, the subgroup of Ras association domain family 1 isoform A （RASSF1A） methylation in ctDNA and the subgroup of the combined alpha‐fetoprotein (AFP) and ctDNA assay. We analyzed the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) as well as the area under the curve (AUC). Results A total of 33 qualified articles with 4113 subjects were incorporated into our meta‐analysis. The combined SEN, SPE, and DOR in quantitative studies were 0.722 (95% confidence interval (95% CI): 0.686‐0.756), 0.823 (95% CI: 0.789‐0.854), 18.532 (95% CI: 8.245‐41.657), respectively, yielding an AUC of 0.880. For qualitative studies, the corresponding value was 0.568 (95% CI: 0.548‐0.587), 0.882 (95% CI: 0.867‐0.897), 10.457 (95% CI: 7.270‐15.040) and 0.787, respectively. Detection of RASSF1A methylation yielded an AUC of 0.841, with a SEN of 0.644 (95% CI: 0.608‐0.678) and a SPE of 0.875 (95% CI: 0.847‐0.900). AFP combined with ctDNA assay achieved an AUC of 0.944, with a SEN of 0.760 (95% CI: 0.728‐00.790) and a SPE of 0.920 (95% CI: 0.893‐00.942). Conclusion Circulating tumor DNA displays a promising diagnostic potential in HCC. However, it is not independently sufficient and can serve as an assistant tool combined with AFP for HCC screening and detection.

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Section: Resultsmentioning

confidence: 99%

Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

et al. 2019

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“…Previously, other researchers have reported dramatic loss of MT expression in primary human HCC by immunohistochemistry methods . Recently, MT1M promoter methylation was reported as biomarkers for HCC or breast cancer . Majumder's group reported that MT1 and MT2 double knockout accelerates hepatocarcinogenesis in mice exposed to the carcinogen diethylnitrosamine .…”

Section: Discussionmentioning

confidence: 99%

“…[18][19][20] Recently, MT1M promoter methylation was reported as biomarkers for HCC or breast cancer. 21,22 Majumder's group reported that MT1 and MT2 double knockout accelerates hepatocarcinogenesis in mice exposed to the carcinogen diethylnitrosamine. 23 Mao's group reported that frequent downregulation of MT1M in human HCC may contribute to liver tumorigenesis by increasing cellular NF-κB activity.…”

Section: Discussionmentioning

confidence: 99%

MiR‐24‐3p enhances cell growth in hepatocellular carcinoma by targeting metallothionein 1M

Dong

Ding

et al. 2016

Cell Biochemistry & Function

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Dysregulation of microRNAs has been demonstrated to contribute to malignant progression of cancers, including hepatocellular carcinoma (HCC). MiR-24-3p was previously reported to be significantly upregulated in HCC. However, the potential role and mechanism of action of miR-24-3p in the initiation and progression of HCC remain largely unknown. Quantitative reverse transcription polymerase chain reaction demonstrated that miR-24-3p was significantly upregulated in HCC tumor tissues compared with nontumor tissues. The cell viability, colony formation assay, and tumorigenicity assays in nude mice showed that miR-24-3p could enhance HCC cell growth in vitro and in vivo. Metallothionein 1M was verified as an miR-24-3p target gene by using dual-luciferase reporter assays, quantitative reverse transcription polymerase chain reaction, and Western blotting, which was involved in miR-24-3p regulated HCC cell growth. These results indicated that miR-24-3p plays an important role in the initiation and progression of HCC by targeting metallothionein 1M, and the miR-24-3p/metallothionein 1M pathway may contribute to the development of novel therapeutic strategies for HCC in the future.

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“…[56] It has been suggested that MT downregulation in cancer is related to promoter hypermethylation as previously shown in hepatoma. [57] It can thus be hypothesized that hypermethylation of the MT promoter may also occur in PCs, leading to a decrease in MT-mediated removal of free radicals, which may cause DNA damage and trigger cancer initiation. However, it has also been shown that MTs contribute to drug resistance in cancers.…”

Section: Resultsmentioning

confidence: 99%

Genetic aspects of pituitary carcinoma

2016

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Background:Pituitary carcinoma (PC) is a rare type of malignant intracranial neoplasm defined as distant metastasis of pituitary adenoma (PA). Although PC incidence is low because only 0.1% to 0.2% of PAs ultimately develop into PCs, the prognosis is poor and 66% of patients die within the first year. Existing therapeutic measures, including surgical removal, chemotherapy, and radiotherapy, have limited effectiveness. The lack of efficacy of current treatments is largely caused by the limited understanding of the molecular pathogenesis of PA and the malignant transformation to PC. Therefore, the aim of this systematic review was to summarize published research regarding gene and protein expression in PC to clarify the molecular mechanisms underlying PC genesis and development and identify new candidate diagnostic biomarkers and therapeutic targets for potential use in personalized treatment of PC.Methods:We followed the PRISMA guidelines to plan and conduct this systematic review. PubMed, Embase, and Web of Science databases were searched for relevant studies conducted before December 16, 2015 describing the association of PC with gene expression at the mRNA and protein levels. MeSH terms combined with free terms were used to retrieve the references.Results:In total, 207 records were obtained by primary search, and 32 were included in the systematic review. Compared with normal pituitary gland and/or PA, 30 and 18 genes were found to have higher or lower expression, respectively, in PCs using different analytical methods. Among them, we selected 9 upregulated and 7 downregulated genes for further analysis based on their identification as candidate treatment targets in other cancers, potential clinical application, or further research value.Conclusion:Previous studies demonstrated that many genes promote PC malignant transformation, angiogenesis, invasion, metastasis, and recurrence. Although most of these genes and proteins have not been fully analyzed with regard to their downstream mechanisms or potential diagnostic and therapeutic application, they have the potential to become candidate PC biomarkers and/or molecular targets for guiding personalized treatment. Modern advanced technologies should be utilized in future research to identify more candidate genes for PC pathogenesis, as precisely targeted gene therapies against PC are urgently required.

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MT1MandMT1Gpromoter methylation as biomarkers for hepatocellular carcinoma

Abstract: MT1M and MT1G promoter methylation may be used as serum biomarkers for noninvasive detection of HCC.

Cited by 65 publications

References 32 publications

Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

MiR‐24‐3p enhances cell growth in hepatocellular carcinoma by targeting metallothionein 1M

Genetic aspects of pituitary carcinoma

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