DNA methylation analysis of selected genes for the detection
of early-stage lung cancer using circulating cell-free DNA

Yang, Zhiping; Qi, Weibo; Sun, Li; Zhou, Hui; Zhou, Biliu; Hu, Yi

doi:10.17219/acem/84935

Cited by 39 publications

(30 citation statements)

References 24 publications

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“…In addition, the methylation status of HOXA9 was considered relevant for subtyping lung cancer using liquid biopsies [110] or for its early detection in circulating cell-free DNA [58]. HOXA9 hypermethylation was also found to be a tool to identify advanced neck squamous cell carcinomas favoring tumor progression and metastasis [57], predict survival in breast cancer patients, together with HOXA10 hypermethylation [111], and detect early onset of endometrial cancer [58].…”

Section: Hoxa Genes Methylated In Cancermentioning

confidence: 99%

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Paço¹,

Garcia

Freitas

2020

Cells

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HOX genes are commonly known for their role in embryonic development, defining the positional identity of most structures along the anterior–posterior axis. In postembryonic life, HOX gene aberrant expression can affect several processes involved in tumorigenesis such as proliferation, apoptosis, migration and invasion. Epigenetic modifications are implicated in gene expression deregulation, and it is accepted that methylation events affecting HOX gene expression play crucial roles in tumorigenesis. In fact, specific methylation profiles in the HOX gene sequence or in HOX-associated histones are recognized as potential biomarkers in several cancers, helping in the prediction of disease outcomes and adding information for decisions regarding the patient’s treatment. The methylation of some HOX genes can be associated with chemotherapy resistance, and its identification may suggest the use of other treatment options. The use of epigenetic drugs affecting generalized or specific DNA methylation profiles, an approach that now deserves much attention, seems likely to be a promising weapon in cancer therapy in the near future. In this review, we summarize these topics, focusing particularly on how the regulation of epigenetic processes may be used in cancer therapy.

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Section: Hoxa Genes Methylated In Cancermentioning

confidence: 99%

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Paço¹,

Garcia

Freitas

2020

Cells

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“…Recently, using integrated methylome analysis Wei et al reported hypermethylation of SPG20, a putative STAT3 target, for non-invasive detection of gastric cancer at an early stage (Wei et al, 2019). Yang et al explored the potential of eight gene panel for non-invasive detection of lung cancer using qMSP and revealed that the promoter methylation of any of the eight gene could detect the disease with a sensitivity of 72% with 91% specificity, reflecting the utility of plasma DNA methylation as a novel approach for detection of lung cancer at early stage (Yang et al, 2018).…”

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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“…19,20 Many studies reported that abnormal DNA methylation correlates with tumor aggressiveness, tumor stage, and prognosis. [21][22][23] Aberrant DNA methylations in plasma are emerging biomarkers for liquid biopsy. In this study, we evaluated whether the detection of SHOX2 and PTGER4 methylation levels in serum would benefit the differential diagnosis of lung nodule found in LDCT screening.…”

Section: Discussionmentioning

confidence: 99%

A Novel Diagnosis Method Based on Methylation Analysis of SHOX2 and Serum Biomarker for Early Stage Lung Cancer

Huang

Zhang

et al. 2020

Cancer Control

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Objectives: Lung cancer (LC) is often accompanied by significant methylation abnormalities. This study aimed to develop a decision tree (DT) accompanied the stature homeobox 2 gene (SHOX2) / prostaglandin E receptor 4 (PTGER4) gene DNA methylation with traditional tumor marker in the differential diagnosis of benign and malignant lung nodule. Methods: We performed a study with 104 patients enrolled in the LC group and 36 patients in the benign lung diseases group. All the clinical data of these patients were collected through electronic medical record. Total Methylation (TM) status of both SHOX2 and PTGER4 was defined as methylation levels of SHOX2 plus methylation levels of PTGER4. One-way analysis was used to compare the concentrations of serum samples and t-test was used to compare pairwise mean values between groups. Receiver operating curve (ROC) was used to evaluate the diagnostic value. Furthermore, the strategy was validated in 19 LC patients and 11 patients with benign lung diseases. Results: There were significant differences between the concentration of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA21 -1) and the methylation levels of SHOX2, PTGER4 and TM in lung benign diseases and cancer group. The AUCs of NSE, CEA, CYFRA21 -1, Methylation SHOX2, Methylation PTGER4 and TM were 0.721 (95% CI: 0.627–0.816), 0.753 (95% CI: 0.673–0.833) and 0.778(95% CI: 0.700–0.856), 0.851(0.786-0.916), 0.847(0.780-0.913) and 0.861(0.800-0.922) respectively. We developed a DT model with TM and CYFRA21 -1 used in this study, and the area under the curve (AUC) of DT was 0.921 and the sensitivity up to 0.856. In the validation cohort, the AUC of SHOX2, PTGER4 and TM was also much higher than traditional serum markers. Conclusions: Our results indicated that the DT model calculated from the TM and CYFRA21 -1 can accurately classify LC and benign diseases, which showed better diagnostic performance than traditional serum parameter.

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DNA methylation analysis of selected genes for the detection of early-stage lung cancer using circulating cell-free DNA

Abstract: analysis of selected genes for the detection of early-stage lung cancer using circulating cell-free DNA.

Cited by 39 publications

References 24 publications

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Epigenetic Biomarkers in the Management of Ovarian Cancer: Current Prospectives

A Novel Diagnosis Method Based on Methylation Analysis of SHOX2 and Serum Biomarker for Early Stage Lung Cancer

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