{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T04:46:41Z","timestamp":1791694001458,"version":"4.3.4"},"reference-count":34,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82273422 for Y.L."],"award-info":[{"award-number":["No. 82273422 for Y.L."]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["No. 82273422 for Y.L."],"award-info":[{"award-number":["No. 82273422 for Y.L."]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Objective: This study evaluated the diagnostic value of a combined SHOX2 and RASSF1A methylation assay (LungMe\u00ae) in differentiating malignant from benign pleural and peritoneal effusions. Methods: A total of 696 patients with pleural or peritoneal effusions were prospectively enrolled. Effusion sediment samples were analyzed by liquid-based cytology (TCT), cell block histology, and methylation-specific PCR for both SHOX2 and RASSF1A. The final diagnosis was confirmed by clinical, imaging, and pathological follow-up. Results: Lung cancer was the predominant cause of malignant pleural effusions (71.96%), while malignant peritoneal effusions mainly resulted from ovarian, gastric, and liver cancers. The optimal \u0394Ct cutoffs for SHOX2 and RASSF1A were \u0394Ct \u2264 9 and \u0394Ct \u2264 12, respectively. The combined methylation assay achieved a sensitivity of 79.1% and specificity of 90.4% for malignant effusions. When combined with cytology, the overall sensitivity increased from 34.7% (TCT alone) to 91.7%, with a positive predictive value (PPV) of 93.9% and a negative predictive value (NPV) of 86.7%. The assay showed high sensitivity across multiple tumor types, including 100% for esophageal and breast cancers, and \u226580% for lung cancer, gastric cancer, lymphoma, and cholangiocarcinoma. Conclusions: The combined SHOX2 and RASSF1A methylation assay has high diagnostic value for benign\u2013malignant discrimination of pleural and peritoneal effusions, improving diagnostic sensitivity when combined with conventional cytology. Thus, within the context of this single-center study, the LungMe\u00ae assay demonstrates promise in expanding pan-cancer diagnostics, but will require further multicenter external validation and prospective clinical studies before routine clinical adoption.<\/jats:p>","DOI":"10.3390\/cancers18193176","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:43:24Z","timestamp":1790880204000},"page":"3176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Dual-Marker DNA Methylation Assay Enables High-Sensitivity Detection of Malignant Effusions Across Cancer Types"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4784-8290","authenticated-orcid":false,"given":"Ting","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Jinshui District, Zhengzhou 450008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9723-8120","authenticated-orcid":false,"given":"Ting","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2865-0192","authenticated-orcid":false,"given":"Matthew","family":"Kafarski","sequence":"additional","affiliation":[{"name":"Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, No. 20 Xisi Road, Chongchuan District, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Xing","sequence":"additional","affiliation":[{"name":"Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Jinshui District, Zhengzhou 450008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"She","sequence":"additional","affiliation":[{"name":"Director of Pathology Business Unit, Shanghai ZJ Bio-Tech CO., Ltd., Building 9, No. 2168 Chenhang Hwy, Shanghai 201114, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosha","family":"Ren","sequence":"additional","affiliation":[{"name":"Director of Pathology Business Unit, Shanghai ZJ Bio-Tech CO., Ltd., Building 9, No. 2168 Chenhang Hwy, Shanghai 201114, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School, 142 Boren Street, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushi","family":"Lin","sequence":"additional","affiliation":[{"name":"Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-9848","authenticated-orcid":false,"given":"Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-5293","authenticated-orcid":false,"given":"Liang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Brown University Warren Alpert Medical School, 142 Boren Street, Providence, RI 02912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Jinshui District, Zhengzhou 450008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqun","family":"Dong","sequence":"additional","affiliation":[{"name":"Precision Health Program, Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4571-2226","authenticated-orcid":false,"given":"Yifei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong 226001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.jphys.2025.06.009","article-title":"Physiotherapy management of pleural effusion","volume":"71","author":"Elkins","year":"2025","journal-title":"J. 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