Diagnostic performance of SHOX2 and RASSF1A gene methylation assays in malignant pleural effusion: A systematic review and meta-analysis

IF 2.6 3区医学 Q3 ONCOLOGY

Cancer Cytopathology Pub Date : 2025-07-04 DOI:10.1002/cncy.70031

Mohamed Smail Aissani MD, Kyrillos Mahrous Gerges MD, Ahmed Msherghi MD, Hajer Farrara MD, Dawood Alatefi MD, Imane Chenfouh MD, Arwi Omar Kara MBBCh, Maram Abuajamieh MBBCh, Ghada Kareem MBBCh, Mohammed Benhammou MD, Mohamed E. Ali MD, Max Wintermark MD, MAS, Muhammed Elhadi MBBCh, MSc

{"title":"Diagnostic performance of SHOX2 and RASSF1A gene methylation assays in malignant pleural effusion: A systematic review and meta-analysis","authors":"Mohamed Smail Aissani MD, Kyrillos Mahrous Gerges MD, Ahmed Msherghi MD, Hajer Farrara MD, Dawood Alatefi MD, Imane Chenfouh MD, Arwi Omar Kara MBBCh, Maram Abuajamieh MBBCh, Ghada Kareem MBBCh, Mohammed Benhammou MD, Mohamed E. Ali MD, Max Wintermark MD, MAS, Muhammed Elhadi MBBCh, MSc","doi":"10.1002/cncy.70031","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <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 <i>SHOX2</i> (short-stature homeobox 2) and <i>RASSF1A</i> (Ras association domain family member 1A) genes in detecting MPE.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>A systematic review and meta-analysis included studies that compared benign pleural effusion and MPE cohorts using methylation of <i>SHOX2</i> and <i>RASSF1A</i> genes in pleural fluid as the index test and cytology/histopathology as the reference standard. A random-effects model was used to calculate sensitivity, specificity, predictive values, and diagnostic odds ratios. Subgroup analysis assessed performance in lung-predominant versus nonlung-predominant MPE.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Four studies with a total of 534 participants were included. The pooled sensitivity and specificity were 85% (95% confidence interval [CI], 53%–96%; heterogeneity [I<sup>2</sup>] = 0.00%) and 92% (95% CI, 88%–95%; I<sup>2</sup> = 24.8%), respectively. The positive and negative predictive values were 93% (95% CI, 85%–97%; I<sup>2</sup> = 61.5%) and 84% (95% CI, 53%–96%; I<sup>2</sup> = 0.00%), respectively. The diagnostic odds ratio was 22.78 (95% CI, 11.00–47.17; I<sup>2</sup> = 25.8%). Subgroup analysis showed a slight decrease in sensitivity (70%; 95% CI, 64%–76%; I<sup>2</sup> = 0.00%) and specificity (91%; 95% CI, 86%–94%; I<sup>2</sup> = 26.1%) when excluding the study with a lung cancer-predominant population.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The combined analysis of <i>SHOX2</i> and <i>RASSF1A</i> 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.</p>\n </section>\n </div>","PeriodicalId":9410,"journal":{"name":"Cancer Cytopathology","volume":"133 8","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cncy.70031","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cytopathology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cncy.70031","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

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 SHOX2 (short-stature homeobox 2) and RASSF1A (Ras association domain family member 1A) genes in detecting MPE.

Methods

A systematic review and meta-analysis included studies that compared benign pleural effusion and MPE cohorts using methylation of SHOX2 and RASSF1A genes in pleural fluid as the index test and cytology/histopathology as the reference standard. A random-effects model was used to calculate sensitivity, specificity, predictive values, and diagnostic odds ratios. Subgroup analysis assessed performance in lung-predominant versus nonlung-predominant MPE.

Results

Four studies with a total of 534 participants were included. The pooled sensitivity and specificity were 85% (95% confidence interval [CI], 53%–96%; heterogeneity [I²] = 0.00%) and 92% (95% CI, 88%–95%; I² = 24.8%), respectively. The positive and negative predictive values were 93% (95% CI, 85%–97%; I² = 61.5%) and 84% (95% CI, 53%–96%; I² = 0.00%), respectively. The diagnostic odds ratio was 22.78 (95% CI, 11.00–47.17; I² = 25.8%). Subgroup analysis showed a slight decrease in sensitivity (70%; 95% CI, 64%–76%; I² = 0.00%) and specificity (91%; 95% CI, 86%–94%; I² = 26.1%) when excluding the study with a lung cancer-predominant population.

Conclusions

The combined analysis of SHOX2 and RASSF1A 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.

Abstract Image

查看原文本刊更多论文

SHOX2和RASSF1A基因甲基化检测在恶性胸腔积液中的诊断价值：一项系统综述和荟萃分析

背景：恶性胸腔积液（MPE）是晚期恶性肿瘤的常见并发症，需要与良性胸腔积液鉴别以进行适当的治疗。细胞学和活组织检查有局限性，需要更敏感、侵入性更小的诊断技术。本研究的目的是评估甲基化SHOX2 （short-身材同源盒2）和RASSF1A （Ras关联结构域家族成员1A）基因在检测MPE中的诊断准确性。方法系统回顾和荟萃分析纳入了以胸膜液中SHOX2和RASSF1A基因甲基化为指标，细胞学/组织病理学为参考标准，比较良性胸腔积液和MPE队列的研究。随机效应模型用于计算敏感性、特异性、预测值和诊断优势比。亚组分析评估肺显性与非肺显性MPE的表现。结果纳入4项研究，共534名受试者。合并敏感性和特异性为85%(95%置信区间[CI]， 53%-96%；异质性[I2] = 0.00%)和92% (95% CI, 88%-95%；I2 = 24.8%)。阳性和阴性预测值分别为93% (95% CI, 85%-97%；I2 = 61.5%)和84% (95% CI, 53%-96%；I2 = 0.00%)。诊断优势比为22.78 (95% CI, 11.00-47.17；i2 = 25.8%)。亚组分析显示敏感性略有下降(70%；95% ci, 64%-76%；I2 = 0.00%)和特异性(91%；95% ci, 86%-94%；I2 = 26.1%)，排除肺癌主要人群的研究。结论SHOX2和RASSF1A甲基化的联合分析在MPE检测中具有很好的诊断准确性，优于细胞学。这种侵入性较小的方法可以减少对侵入性较大的手术的依赖，尽管需要进一步的研究来证实其对不同人群和癌症类型的有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cancer Cytopathology 医学-病理学

CiteScore

7.00

自引率

17.60%

发文量

130

审稿时长

1 months

期刊介绍： Cancer Cytopathology provides a unique forum for interaction and dissemination of original research and educational information relevant to the practice of cytopathology and its related oncologic disciplines. The journal strives to have a positive effect on cancer prevention, early detection, diagnosis, and cure by the publication of high-quality content. The mission of Cancer Cytopathology is to present and inform readers of new applications, technological advances, cutting-edge research, novel applications of molecular techniques, and relevant review articles related to cytopathology.