Diagnostic Performance of BUU-Customized Whole-Exome Sequencing for Suspicious Thyroid Nodules: A Prospective Diagnostic Accuracy Study
Narit Jianbunjongkit, Apinya Jusakul, Kanchana Suksri, Alisara Wongsuttilert, Nattawut Amornpinyokiat, Watchareporn Teeramatwanich, Krongchai Kasemsrithanawat, Pattaravadee SrikoonImportance:
Suspicious thyroid nodules often prompt avoidable surgeries due to diagnostic uncertainty. Although commercial next-generation sequencing assays improve risk stratification, evidence for locally developed sequencing pipelines remains limited.
Objective:
To evaluate the diagnostic performance of Burapha University-customized whole-exome sequencing (BUU-WES) using preoperative ultrasound-guided core needle biopsy (CNB) specimens, with postsurgical histopathology as the reference standard.
Design:
Multicenter prospective diagnostic accuracy study.
Setting:
Four tertiary-care hospitals in Thailand.
Participants:
Adults (≥20 years) undergoing thyroid surgery for nodules suspicious on ultrasonography (American College of Radiology Thyroid Imaging Reporting and Data System 4-5) and/or cytology (Bethesda I-V).
Intervention:
DNA extracted from CNB specimens underwent BUU-WES; variants were interpreted using curated databases and published evidence.
Main Outcome and Measures:
Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy with 95% confidence intervals (CIs).
Results:
Among 82 participants (82 index nodules), malignancy prevalence was 25.6% (21/82). BUU-WES demonstrated sensitivity of 57.1% (95% CI, 34.0%-78.2%), specificity of 86.9% (95% CI, 75.8%-94.2%), PPV of 60.0% (95% CI, 36.1%-80.9%), and NPV of 85.5% (95% CI, 74.2%-93.1%). In nodules ≥1 cm (n = 71), sensitivity increased to 83.3% (95% CI, 51.6%-97.9%), specificity 89.8% (79.2%-96.2%), with NPV 96.4% (95% CI, 87.5%-99.6%). In indeterminate cytology (Bethesda III/IV), BUU-WES showed moderate diagnostic performance, with sensitivity of 60% and specificity and NPV of 86.4%. The most frequently detected alterations involved
Conclusions:
BUU-WES primarily functions as a rule-in test due to its high specificity. Its most clinically relevant application is in indeterminate thyroid nodules (Bethesda III/IV), where it serves as an adjunctive tool for risk stratification. Within this subgroup, diagnostic performance is further optimized in nodules ≥1 cm, where the improved NPV suggests potential rule-out applicability in appropriately selected patients.