Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study

Qiao, Guibin; Zhuang, Weitao; Dong, Bo; Li, Chengcheng; Xu, Jiayue; Wang, Guoqiang; Xie, Liang; Zhou, Zihao; Tian, Dan; Chen, Gang; Tang, Jiming; Zhou, Haiyu; Zhang, Dongkun; Shi, Ruiqing; Chen, Rixin; Nian, Weiqi; Zhang, Yuzi; Zhao, Jing; Wen, Xiaofang; Xu, Yu; Li, Bingsi; Cai, Shangli; Ben, Xiaosong; Qi, Yu

doi:10.1186/s12916-021-02109-y

Cited by 26 publications

(18 citation statements)

References 26 publications

(28 reference statements)

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“…They tested the model in three independent cohorts and achieved good sensitivities (74.7%–86.0%) and specificities (94.0%–95.9%) ( Qiao et al, 2021 ). However, the sensitivity of this diagnostic model for stage 0-II esophageal cancer was only 58.8% ( Qiao et al, 2021 ).…”

Section: Dna Methylation In Bloodmentioning

confidence: 99%

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: Dna Methylation In Bloodmentioning

confidence: 99%

DNA methylation markers in esophageal cancer

Xu,

Wang,

Pei

et al. 2024

Front. Genet.

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“…More recently, some studies have demonstrated the clinical value of circulating tumor DNA (ctDNA) for EC [ 11 , 12 ]. The ctDNA is defined as cell free DNA (cfDNA) released by necrotic and apoptotic cancer cells into the blood; and its diagnostic, therapeutic, and prognostic value have been widely studied.…”

Section: Introductionmentioning

confidence: 99%

An update of clinical value of circulating tumor DNA in esophageal cancer: a systematic review and meta-analysis

Zhang,

Du,

Wang

et al. 2024

BMC Cancer

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Background Esophageal cancer (EC) is a deadly disease with limited therapeutic options. Although circulating tumor DNA (ctDNA) could be a promising tool in this regard, the availiable evidence is limited. We performed a systematic review and meta-analysis to summarize the clinical applicability of the next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) technology on the ctDNA detection of the EC and listed the current challenges. Methods We systematically searched MEDLINE (via PubMed), Embase (via OVID), ISI Web of Science database and Cochrane Library from January, 2000 to April, 2023. Progression-free survival (PFS) and overall survival (OS) were set as primary outcome endpoints. Pathologic response was evaluated by tumor regression grade (TRG), according to the eighth edition of the American Joint Committee on Cancer (AJCC). Major pathologic regression (MPR) was defined as TRG 1 and 2. The MPR was set as secondary endpoint. Hazard rate (HR) and associated 95% CI were used as the effect indicators the association between ctDNA and prognosis of EC. MPR rates were also calculated. Fixed-effect model (Inverse Variance) or random-effect model (Mantel-Haenszel method) was performed depending on the statistically heterogeneity. Results Twenty-two studies, containing 1144 patients with EC, were included in this meta-analysis. The results showed that OS (HR = 3.87; 95% CI, 2.86–5.23) and PFS (HR = 4.28; 95% CI, 3.34–5.48) were shorter in ctDNA-positive patients. In the neoadjuvant therapy, the sensitivity analysis showed the clarified HR of ctDNA-positive was 1.13(95% CI, 1.01–1.28). We also found that TP53, NOTCH1, CCND1 and CNKN2A are the most frequent mutation genes. Conclusions Positive ctDNA is associated with poor prognosis, which demonstrated clinical value of ctDNA. Longitudinal ctDNA monitoring showed potential prognostic value in the neoadjuvant therapy. In an era of precision medicine, ctDNA could be a promising tool to individualize treatment planning and to improve outcomes in EC. PROSPERO registration number CRD42023412465.

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“…Esophageal cancer is among the leading causes of cancer-related deaths worldwide [ 1 , 2 , 3 ]. The current mainstream treatments for esophageal cancer include esophagectomy, chemotherapy, radiotherapy, targeted therapy, multimodal therapy and recently, immunotherapy [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Glutamine Deprivation Synergizes the Anticancer Effects of Cold Atmospheric Plasma on Esophageal Cancer Cells

et al. 2023

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Esophageal cancer is a highly aggressive malignancy with a low response to standard anti-cancer therapies. There is an unmet need to develop new therapeutic strategies to improve the clinical outcomes of current treatments. Cold atmospheric plasma (CAP) is a promising approach for cancer treatment, and has displayed anticancer efficacy in multiple preclinical models. Recent studies have shown that the efficacy of CAP is positively correlated with intracellular reactive oxygen species (ROS) levels. This suggests that aggressively increasing intracellular ROS levels has the potential to further improve CAP-mediated anticancer efficacy. Glutamine plays an important role in cellular ROS scavenging after being converted to glutathione (GSH, a well-described antioxidant) under physiological conditions, so reducing intracellular glutamine levels seems to be a promising strategy. To test this hypothesis, we treated esophageal cancer cells with CAP while controlling the supply of glutamine. The results showed that glutamine did affect the anticancer effect of CAP, and the combination of CAP stimulation and glutamine deprivation significantly inhibited the proliferation of esophageal cancer cells compared to the control group (p < 0.05). Furthermore, flow cytometric analysis documented a significant increase in more than 10% in apoptosis and necrosis of esophageal cancer cells after this synergistic treatment compared to the control group (p < 0.05). Thus, these results provide the first direct evidence that the biological function of CAP can be modulated by glutamine levels and that combined CAP stimulation and glutamine deprivation represent a promising strategy for the future treatment of esophageal cancer.

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Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study

Cited by 26 publications

References 26 publications

DNA methylation markers in esophageal cancer

DNA methylation markers in esophageal cancer

An update of clinical value of circulating tumor DNA in esophageal cancer: a systematic review and meta-analysis

Glutamine Deprivation Synergizes the Anticancer Effects of Cold Atmospheric Plasma on Esophageal Cancer Cells

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