ArticleClinical epigenetics2025
Diagnostic efficacy and subgroup heterogeneity of SHOX2, RASSF1A, Septin9, and HOXA9 methylation in pleural effusion lymphoma.
Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDNA methylation profiling has emerged as a promising tool for improving pathological diagnosis. This study investigates the diagnostic efficacy and subgroup heterogeneity of SHOX2, RASSF1A, Septin9, and HOXA9 methylation in pleural effusion lymphoma, aiming to enhance diagnostic accuracy and identify high-risk molecular subgroups.
methodsA cohort of 109 patients (73 lymphoma, 36 benign pleural effusions) was analyzed using quantitative methylation-specific PCR for the four biomarkers. Receiver operating characteristic (ROC) curves were constructed to determine optimal cutoff values for each marker, and their diagnostic performance was evaluated in different lymphoma subgroups.
resultsThe cycle threshold values for the internal control β-actin predominantly ranged from 18 to 23, suggesting consistent DNA input for methylation analysis. ROC curve revealed that the area under the curve (AUC) values were 0.871 (SHOX2), 0.779 (HOXA9), 0.611 (Septin9), and 0.548 (RASSF1A). When combined, the four markers achieved an AUC of 0.896, with an overall diagnostic sensitivity of 83.6% and a specificity of 94.4%. SHOX2 and HOXA9 demonstrated higher sensitivity within diffuse large B-cell lymphoma (DLBCL) subgroups, with SHOX2 achieving 100% sensitivity in the non-GCB subgroup and HOXA9 achieving 90.9% sensitivity in the GCB subgroup. Septin9 methylation was significantly associated with the presence of B symptoms (P = 0.041). Importantly, RASSF1A methylation was more strongly associated with TP53 deletion rather than with Bcl-2/IGH, Bcl-6, or c-MYC rearrangements.
conclusionIntegrating methylation markers SHOX2, HOXA9, Septin9, and RASSF1A exhibits significant diagnostic potential in pleural effusion lymphoma, especially within DLBCL subgroups. These markers could prove valuable in identifying high-risk subgroups and guiding clinical decision-making.
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