Genome-Wide Plasma Cell-Free DNA Methylation Profiling Identifies Potential Biomarkers for Lung Cancer

Xu, Wei; Lü, Jun; Zhao, Qiang; Wu, Jun; Sun, Jingyong; Han, Baohui; Zhao, Xiaodong; Kang, Yani

doi:10.1155/2019/4108474

Cited by 41 publications

(35 citation statements)

References 35 publications

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“…For SLC9A3R2 gene, previous studies have proven that this gene is involved in the colon cancer [35] and breast cancer [36] . In addition, the aberrant methylation status of SLC9A3R2 in cell free-DNA could be a potential biomarker for lung cancer [37] . However, the study of both SLC9A3R2 and ZC3H3 in liver cancer is lacked.…”

Section: Discussionmentioning

confidence: 99%

Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients

Fan

et al. 2020

Neoplasia

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Aberrant methylation is a hallmark of hepatocellular carcinoma and plays an important role in tumor initiation and progression. However, the epigenome-wide methylation patterns of portal vein tumor thrombosis (PVTTs) have not been fully explored. Here, we performed epigenome-wide DNA methylation of adjacent normal tissues (ANTs), paired tumor tissues and paired PVTTs using an Infinium HumanMethylation450 array ( n = 11) and conducted the Sequenom EpiTYPER assays to confirm the aberrantly methylated genes. MTS and apoptosis assay were used to assess the synergistic effect of two drugs on the HCC cell lines. We found the mean global methylation levels of HCC tissues and PVTTs were significantly lower than ANTs ( P < 0.01). A total of 864 differentially methylated CpG sites annotated in 532 genes were identified between HCC tissues and paired PVTTs (|mean methylation difference|>10%, P < 0.005). The pathway analysis based on hypermethylated genes in PVTT tissues was interestingly enriched in regulation of actin cytoskeleton pathway ( P = 4.48E−5). We found 23 genes whose methylation levels were gradually alternated in HCC tissues and PVTTs. Aberrant methylation status of TNFRSF10A, ZC3H3 and SLC9A3R2 were confirmed in a validation cohort ( n = 48). The functional experiments demonstrated the combination of decitabine (DAC) and tumor necrosis factor-related apoptosis-inducing ligand (rh-TRAIL) could synergistically suppress the proliferation and induce apoptosis in SK-Hep-1 and Huh7 cell lines. Together, our findings indicated that DNA methylation plays an important role in the PVTT formation through regulating the metastasis-related pathways. The combination of DAC and rh-TRAIL might be a promising treatment strategy for HCC.

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Section: Discussionmentioning

confidence: 99%

Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients

Fan

et al. 2020

Neoplasia

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“…Other studies using genome-wide methylation profiling of serum/plasma cell-free DNA have identified potential biomarkers for clinical utility. For instance, Xu et al using MeDIP-seq approach reported 10 significant differentially methylated genes as potent biomarker for lung cancer clinical application (Xu et al, 2019). Similarly, using genome-wide methylome profiling and Sequenom MassARRAY approach, it was reported that promoter methylation of CASZ1, CDH13, and ING2 could serve as a potent noninvasive biomarker for detection of esophageal cancer at early stage (Wang H.Q.…”

Section: Clinical Application Of Epigenetic Biomarker In Liquid Biopsmentioning

confidence: 99%

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

Singh

Gupta

Sachan

2019

Front. Cell Dev. Biol.

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Ovarian cancer (OC) causes significant morbidity and mortality as neither detection nor screening of OC is currently feasible at an early stage. Difficulty to promptly diagnose OC in its early stage remains challenging due to non-specific symptoms in the early-stage of the disease, their presentation at an advanced stage and poor survival. Therefore, improved detection methods are urgently needed. In this article, we summarize the potential clinical utility of epigenetic signatures like DNA methylation, histone modifications, and microRNA dysregulation, which play important role in ovarian carcinogenesis and discuss its application in development of diagnostic, prognostic, and predictive biomarkers. Molecular characterization of epigenetic modification (methylation) in circulating cell free tumor DNA in body fluids offers novel, non-invasive approach for identification of potential promising cancer biomarkers, which can be performed at multiple time points and probably better reflects the prevailing molecular profile of cancer. Current status of epigenetic research in diagnosis of early OC and its management are discussed here with main focus on potential diagnostic biomarkers in tissue and body fluids. Rapid and point of care diagnostic applications of DNA methylation in liquid biopsy has been precluded as a result of cumbersome sample preparation with complicated conventional methods of isolation. New technologies which allow rapid identification of methylation signatures directly from blood will facilitate sample-to answer solutions thereby enabling next-generation point of care molecular diagnostics. To date, not a single epigenetic biomarker which could accurately detect ovarian cancer at an early stage in either tissue or body fluid has been reported. Taken together, the methodological drawbacks, heterogeneity associated with ovarian cancer and non-validation of the clinical utility of reported potential biomarkers in larger ovarian cancer populations has impeded the transition of epigenetic biomarkers from lab to clinical settings. Until addressed, clinical implementation as a diagnostic measure is a far way to go.

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“…The B3GAT2 gene is a trans-membrane protein involved in the synthesis of a carbohydrate epitope, a sulfated trisaccharide involved in cellular migration. 32 Although gene sequencing data showed higher expression of the transcript than control, there is scant evidence of B3GAT2's involvement in oocyte maturation. Hence further studies are warranted.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, downregulation of inhibin beta B unit might be due to the action of FSH hormone in in vitro matured COCs. 32 Matured COCs do not require FSH action, providing negative signals to stop the secretion of FSH. 43 CPSF1 is involved in the cleavage of the 3' signaling region from a newly synthesized pre-messenger RNA (pre-mRNA) molecule in the process of gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of in vitro-matured oocytes from a korean native cow (hanwoo) after cysteamine supplementation

Chowdhury

Park

Afrin

et al. 2020

Animal Biotechnology

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This study elucidated the molecular markers that decrease oocyte quality during in vitro culture, restricting optimal developmental potential. Here, we evaluated the transcriptomic differences between cysteamine-treated and non-treated bovine cumulus oocyte complexes (COCs) after 22 h of co-culture in the maturation media using RNA sequencing. In total, 39,014 transcripts were sequenced between cysteamine-treated and non-treated mature COCs. We evaluated the relative expression of 21,472 genes, with 59 genes showing differential expression between the two COC groups. The cysteamine-treated group had 36 upregulated gene transcripts and 23 down-regulated gene transcripts. Moreover, gene ontology (GO) enrichment analysis revealed that multiple biological processes were significantly enriched after cysteamine supplementation. Differentially expressed genes appeared to maintain normal oocyte physiology, regulation of apoptosis, differentiation, ossification or bone formation, cardiac and muscle physiology, hormonal secretion, and membrane construction for further embryonic development. In conclusion, cysteamine affects the mRNA level of COCs during oocyte maturation by upregulating potential molecular markers and downregulating genes that affect further embryonic development.

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Genome-Wide Plasma Cell-Free DNA Methylation Profiling Identifies Potential Biomarkers for Lung Cancer

Cited by 41 publications

References 35 publications

Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients

Epigenome-wide DNA methylation profiling of portal vein tumor thrombosis (PVTT) tissues in hepatocellular carcinoma patients

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

Transcriptome profiling of in vitro-matured oocytes from a korean native cow (hanwoo) after cysteamine supplementation

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