{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T15:57:51Z","timestamp":1791734271727,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Malignant pleural effusion (MPE) is a common complication of advanced malignancies, requiring differentiation from benign pleural effusion for appropriate management. Cytology and biopsy have limitations, necessitating more sensitive, less invasive diagnostic techniques. The objective of this study was to evaluate the diagnostic accuracy of methylated <jats:italic>SHOX2<\/jats:italic> (short\u2010stature homeobox 2) and <jats:italic>RASSF1A<\/jats:italic> (Ras association domain family member 1A) genes in detecting MPE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review and meta\u2010analysis included studies that compared benign pleural effusion and MPE cohorts using methylation of <jats:italic>SHOX2<\/jats:italic> and <jats:italic>RASSF1A<\/jats:italic> genes in pleural fluid as the index test and cytology\/histopathology as the reference standard. A random\u2010effects model was used to calculate sensitivity, specificity, predictive values, and diagnostic odds ratios. Subgroup analysis assessed performance in lung\u2010predominant versus nonlung\u2010predominant MPE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four studies with a total of 534 participants were included. The pooled sensitivity and specificity were 85% (95% confidence interval [CI], 53%\u201396%; heterogeneity [I<jats:sup>2<\/jats:sup>]\u00a0=\u00a00.00%) and 92% (95% CI, 88%\u201395%; I<jats:sup>2<\/jats:sup>\u00a0=\u00a024.8%), respectively. The positive and negative predictive values were 93% (95% CI, 85%\u201397%; I<jats:sup>2<\/jats:sup>\u00a0=\u00a061.5%) and 84% (95% CI, 53%\u201396%; I<jats:sup>2<\/jats:sup>\u00a0=\u00a00.00%), respectively. The diagnostic odds ratio was 22.78 (95% CI, 11.00\u201347.17; I<jats:sup>2<\/jats:sup>\u00a0=\u00a025.8%). Subgroup analysis showed a slight decrease in sensitivity (70%; 95% CI, 64%\u201376%; I<jats:sup>2<\/jats:sup>\u00a0=\u00a00.00%) and specificity (91%; 95% CI, 86%\u201394%; I<jats:sup>2<\/jats:sup>\u00a0=\u00a026.1%) when excluding the study with a lung cancer\u2010predominant population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The combined analysis of <jats:italic>SHOX2<\/jats:italic> and <jats:italic>RASSF1A<\/jats:italic> methylation demonstrated promising diagnostic accuracy for MPE detection, outperforming cytology. This less invasive method could reduce reliance on more invasive procedures, although further research is needed to confirm its efficacy across diverse populations and cancer types.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.70031","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T13:36:02Z","timestamp":1751636162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Diagnostic performance of <i>SHOX2<\/i> and <i>RASSF1A<\/i> gene methylation assays in malignant pleural effusion: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"133","author":[{"given":"Mohamed Smail","family":"Aissani","sequence":"first","affiliation":[{"name":"Faculty of Medicine University Blida 01  Blida Algeria"},{"name":"Ibrahime Tirichine Public Hospital  Blida 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Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-9101","authenticated-orcid":false,"given":"Imane","family":"Chenfouh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy  Oujda, Oujda\u2010Angad Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arwi Omar","family":"Kara","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Benghazi  Benghazi Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram","family":"Abuajamieh","sequence":"additional","affiliation":[{"name":"Cairo University School of Medicine  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Kareem","sequence":"additional","affiliation":[{"name":"Department of Medicine Faculty of Medicine Al\u2010Qadisiyah University  Diwaniyah 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