Accurate Nonendoscopic Detection of Esophageal Squamous Cell Carcinoma Using Methylated DNA Biomarkers

Ma, Ke; Kalra, Andrew; Tsai, Hua‐Ling; Okello, Samson; Cheng, Yulan; Meltzer, Stephen J.; Lumori, Boniface Amanee Elias; Opio, Christopher; Jit, Simran; Danilova, Ludmila; Wang, Zhe; Şimşek, Halis; Ngamruengphong, Saowanee; Shin, Eun Ji; Khashab, Mouen A.; Singh, Vikesh K.; Tieu, Alan H.; Nolet, Corey; Gong, Dennis; Chang, Kyungho; Prasath, Vishnu; Bollinger, Robert C.; Wang, Tza‐Huei; Feliciano, Josephine; Lam, Vincent K.; Battafarano, Richard J.; Turner, Michelle; Lang, Peggy; Marrone, Kristen A.; Wang, Hao

doi:10.1053/j.gastro.2022.04.021

Cited by 9 publications

(10 citation statements)

References 14 publications

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“…Therefore, the utilization of esophageal sampling devices still has an approximate noncompliance rate of 10% during the application ( Table 2 ). However, current DNA methylation studies based on the esophageal exfoliated cells mainly focus on EAC and its precursor lesions, with only one study specifically targeting ESCC, and a lack of validation for ESCC precursor lesions ( Ma et al, 2022 ). ESCC constitutes the majority of EC cases ( Yang et al, 2020 ), making it essential to pay more attention to the methylation analysis using esophageal exfoliated cells in ESCC in future research.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, aside from BE, there is another feasibility study that utilizes EsophaCap for sample collection and early diagnosis of ESCC. This study developed a 3-marker panel ( cg20655070 , SLC35F1 , and ZNF132 ) with sensitivities ranging from 86.0% to 92.0% and specificities ranging from 86.0% to 86.7% for ESCC ( Ma et al, 2022 ).…”

Section: Dna Methylation In Esophageal Exfoliated Cellsmentioning

confidence: 99%

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DNA methylation markers in esophageal cancer

Xu,

Wang,

Pei

et al. 2024

Front. Genet.

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BackgroundEsophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection.MethodsTo identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening.FindingsThis review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma.ConclusionIn conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

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Section: Discussionmentioning

confidence: 99%

Section: Dna Methylation In Esophageal Exfoliated Cellsmentioning

confidence: 99%

DNA methylation markers in esophageal cancer

Xu,

Wang,

Pei

et al. 2024

Front. Genet.

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“…Notably, all modules were designed to perform the four-channel on-cartridge assays with consistency, and the thermal module uses a miniaturized heater for accelerating methylation-specific qPCR. As a proof of concept, we employed ACCESS to simultaneously detect two methylation biomarkers from two biomarker genes in esophageal squamous cell carcinoma (ESCC), a subtype of esophageal cancer more frequent in developing countries. − Our findings showcase ACCESS’s potential as a simple, reliable, and affordable tool for esophageal cancer diagnosis in resource-limited settings.…”

Section: Introductionmentioning

confidence: 92%

“…Notably, these aberrant methylation events transpire early in carcinogenesis, often preceding tumor formation, making them ideal markers for early cancer detection. Detection of methylation biomarkers is commonly accomplished through an assay that involves extraction and purification of genomic DNA (gDNA), bisulfite conversion that selectively converts unmethylated cytosines to uracils, and methylation-specific quantitative real-time polymerase chain reaction (qPCR), which selectively amplifies regions containing unconverted methylcytosines. − However, this common assay can be tedious and time-consuming and is predominantly performed manually on a benchtop, by trained personnel within well-equipped laboratories. In addition, manual operation can be susceptible to human error and contamination, which lowers the assay sensitivity and specificity.…”

Section: Introductionmentioning

confidence: 99%

Cancer Methylation Biomarker Detection in an Automated, Portable, Multichannel Magnetofluidic Platform

Hasnain,

Stark,

Trick

et al. 2024

ACS Nano

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Early detection of cancer is critical to improving clinical outcomes, especially in territories with limited healthcare resources. DNA methylation biomarkers have shown promise in early cancer detection, but typical workflows require highly trained personnel and specialized equipment for manual and lengthy processing, limiting use in resource-constrained areas. As a potential solution, we introduce the Automated Cartridge-based Cancer Early Screening System (ACCESS), a compact, portable, multiplexed, automated platform that performs droplet magnetofluidic-and methylation-specific qPCR-based assays for the detection of DNA methylation cancer biomarkers. Development of ACCESS focuses on esophageal cancer, which is among the most prevalent cancers in low-and middle-income countries with extremely low survival rates. Upon implementing detection assays for two esophageal cancer methylation biomarkers within ACCESS, we demonstrated successful detection of both biomarkers from esophageal tumor tissue samples from eight esophageal cancer patients while showing specificity in paired normal esophageal tissue samples. These results illustrate ACCESS's potential as an amenable epigenetic diagnostic tool for resource-constrained areas toward early detection of esophageal cancer and potentially other malignancies.

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“…Notably, liquid biopsy based on blood samples with noninvasive, high sensitivity and speci city features could be a promising tool for LAEC receiving neoadjuvant ICI. Molecular biomarkers such as plasma circulating extracellular vesicles [15,16], methylated DNA [17], circulating tumor cells [18,19], circulating tumor DNA [20], and autoantibodies [21,22] have shown superiority in early diagnosis, monitoring metastasis, and predicting the prognosis of esophageal cancer. Nevertheless, the value of plasma metabolites-based non-invasive biomarkers in predicting the e cacy and prognosis of neoadjuvant ICI for LAEC has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Integrated metabolic and immune profiling analysis reveals distinct prognostic signatures for neoadjuvant immunotherapy in locally advanced esophageal cancer

Liu

Zhao

et al. 2023

Preprint

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Background There is an unmet demand for non-invasive biomarker assays to identify patients benefiting from neoadjuvant immune checkpoint inhibitors (ICIs). Here, we aimed to characterize the composition and alterations in plasma metabolites and peripheral blood immune cell subtypes associated with neoadjuvant ICI efficacy in locally advanced esophageal cancer (LAEC) and to investigate potential novel therapeutic targets and non-invasive biomarkers for predicting ICI efficacy. Methods 89 patients with LAEC treated with neoadjuvant programmed cell death 1 blockade combined with chemotherapy were included in this study. We performed an untargeted metabolomic analysis of 606 metabolites on 72 plasma samples using high-performance liquid chromatography-mass spectrometry and an immune profiling analysis of 9 immune cell subtypes on 33 peripheral blood mononuclear-cell samples using flow cytometry. Furthermore, we conducted correlation network and pathway enrichment analyses for potentially beneficial and pathogenic metabolites to explore the metabolite-mediated ICI responses. Finally, a metabolite-based prediction model was established using the least absolute shrinkage and selection operator regression analysis. Results Comparative metabolomics revealed that pyrimidine and purine metabolic pathways were disturbed in ICI non-responders, with significant enrichment of dihydrothymidine, ureidoisobutyric acid, and deoxyadenosine, which were significantly associated with poor survival. Conversely, jasmonic acid increased dramatically in responders and was significantly associated with better survival. Strikingly, tryptophan metabolism intermediate-indole-3-acetic acid and arachidonic acid metabolism intermediate-16(R)-HETE levels were positively correlated with cytotoxic T lymphocyte levels but inversely correlated with polymorphonuclear-myeloid-derived suppressor cells levels, which were markedly associated with a favorable prognosis. Notably, the area under the receiver operating curve for the metabolite-based model predicting 12-month overall survival was 87.7% and 82.6% in the discovery and validation cohorts, respectively, demonstrating promising performance. Conclusions Our work identified potential non-invasive biomarkers based on plasma metabolic signatures for predicting neoadjuvant ICI responses and prognosis in patients with LAEC, which provides novel insight into ICI precision medicine in the management of LAEC.

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Accurate Nonendoscopic Detection of Esophageal Squamous Cell Carcinoma Using Methylated DNA Biomarkers

Cited by 9 publications

References 14 publications

DNA methylation markers in esophageal cancer

DNA methylation markers in esophageal cancer

Cancer Methylation Biomarker Detection in an Automated, Portable, Multichannel Magnetofluidic Platform

Integrated metabolic and immune profiling analysis reveals distinct prognostic signatures for neoadjuvant immunotherapy in locally advanced esophageal cancer

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