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A diagnostic model was developed by integrating a DNA methylation panel with conventional clinical parameters, deriving seven CpG markers from genome-wide profiling and validating performance across two independent patient cohorts. The integrated model improved accuracy and was formalized as a nomogram, supporting precision oncology and potentially reducing invasive 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","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-25","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",6,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"Why is preoperative diagnosis of upper mediastinal lymph node metastasis important in EGJ adenocarcinoma?","Question",{"text":63,"@type":64},"Upper mediastinal lymph node metastasis is linked to poor prognosis, and current preoperative diagnostic accuracy is inadequate, making treatment planning difficult.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was the methylation panel developed and validated?",{"text":68,"@type":64},"Genome-wide methylation profiling identified seven CpG sites associated with involvement, and the resulting panel was evaluated in two independent cohorts totaling 133 treatment-naïve 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Diagnosis of Upper Mediastinal Lymph Node Metastasis in Esophagogastric Junction Adenocarcinoma  \nYudai Higuchi  | Katsutoshi Shoda | Suguru Maruyama | Yoshihiko Kawaguchi | Takaomi Ozawa | Hiroto Tanaka  | Takashi Nakayama  | Koichi Matsuoka | Ryo Saito | Wataru Izumo | Koichi Takiguchi | Kensuke Shiraishi |  \nShinji Furuya | Hidetake Amemiya | Daisuke Ichikawa  \nFirst Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan Correspondence: Katsutoshi Shoda ([kshoda@yamanashi.ac.jp](kshoda@yamanashi.ac.jp))  \nReceived: 19 May 2025 | Revised: 11 September 2025 | Accepted: 28 September 2025  \nFunding: The authors received no specific funding for this work.  \nKeywords: biomarkers | DNA methylation | esophagogastric junction | lymphatic metastasis | neoplasms  \nABSTRACT  \nEven after surgical resection, the prognosis is poor for patients with esophagogastric junction adenocarcinoma who develop upper mediastinal lymph node metastasis. Moreover, the current preoperative diagnostic accuracy for upper mediastinal lymph node metastasis remains inadequate, which complicates treatment planning. To enhance diagnostic precision and facilitate personalized therapeutic strategies, we aimed to develop a novel diagnostic model that integrates a DNA methylation panel with conventional clinical parameters. First, genome-wide methylation profiling of 69 tumors identified seven CpG sites significantly associated with upper mediastinal lymph node involvement. We then evaluated a methylation panel based on these markers in two independent cohorts comprising a total of 133 treatment-naïve patients. The methylation panel alone achieved moderate diagnostic performance (AUC 0.71, 95% CI 0.52–0.91), whereas its integration with clinical data substantially improved accuracy (training cohort: AUC 0.87, 95% CI 0.75–0.99) . Applying the same model formula to an independent pretreatment validation cohort confirmed its robustness (AUC 0.85, 95% CI 0.70–1.00) . Furthermore, the methylation panel was identified as an independent prognostic factor for overall survival (p \u003C 0.01) . Finally, to facilitate clinical implementation, the integrated model was formalized as a nomogram. In summary, this novel diagnostic model enables highly accurate detection of upper mediastinal lymph node metastasis in esophagogastric junction adenocarcinoma, with the potential to optimize treatment decisions and reduce the need for invasive procedures, thereby contributing to precision oncology.  \n1 | Introduction  \nOver the past few decades, the incidence of esophagogastric junction adenocarcinoma (EGJAC) has increased substantially in Western countries, a trend largely attributed to the declining  \nprevalence of Helicobacter pylori infection along with increasing rates of obesity and gastroesophageal reflux disease. Similar patterns have been observed in several Asian countries [1–4] . Despite significant advancements in surgical techniques, perioperative management, and multidisciplinary therapeutic  \n\n| Abbreviations: ASA-PS, American Society of Anesthesiologists physical status; AUC, area under the curve; BMI, body mass index; bsDNA, bisulfite converted DNA; CT, computed tomography; DMC, differentially methylated CpG site; EGJ, esophagogastric junction; EGJAC, esophagogastric junction adenocarcinoma; FDG, fluorodeoxyglucose; FDG-PET, fluorodeoxyglucose positron emission tomography; FFPE, formalin-fixed paraffin-embedded; HRs, hazard ratios; LASSO, least absolute shrinkage and selection operator; LNM, lymph node metastasis; MDCT, multidetector computed tomography; MSP, methylation-specific quantitative polymerase chain reaction; ROC, receiver operating characteristic; TCGA, The Cancer Genome Atlas; UM, upper mediastinal. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits us","cbCaik8S2KpZFHDu","https://ap.wps.com/l/cbCaik8S2KpZFHDu","pdf",4226384,12,"English","# Abstract\n# Introduction","[{\"question\":\"Why is preoperative diagnosis of upper mediastinal lymph node metastasis important in EGJ adenocarcinoma?\",\"answer\":\"Upper mediastinal lymph node metastasis is linked to poor prognosis, and current preoperative diagnostic accuracy is inadequate, making treatment planning difficult.\"},{\"question\":\"How was the methylation panel developed and validated?\",\"answer\":\"Genome-wide methylation profiling identified seven CpG sites associated with involvement, and the resulting panel was evaluated in two independent cohorts totaling 133 treatment-naïve patients.\"},{\"question\":\"What was the diagnostic benefit of combining methylation data with clinical parameters?\",\"answer\":\"The methylation panel alone showed moderate performance, while integration with clinical data substantially increased diagnostic accuracy in both training and independent validation cohorts.\"},{\"question\":\"How was the integrated model prepared for clinical use?\",\"answer\":\"The integrated model was formalized as a nomogram to support clinical implementation and improve decision-making.\"}]","Novel Methylation-Based Model for Accurate Diagnosis of Upper Mediastinal Lymph Node Metastasis in Esophagogastric Junction Adenocarcinoma | PDF",1790733944]