Evaluating the clinical performance of an updated microRNA classifier in indeterminate and RAS-mutated thyroid nodule...

Area of Science:

• Molecular diagnostics
• Oncology
• Endocrinology

Background:

• MicroRNA markers integrated with next-generation sequencing may improve risk assessment for cytologically indeterminate thyroid nodules.
• The prior ThyGeNEXT-ThyraMIRv1 multiplatform test showed limited utility in stratifying RAS-mutated indeterminate thyroid nodules.
• Validation of the updated ThyraMIRv2 platform in clinical practice was sought.

Purpose of the Study:

• To validate the clinical utility of the updated ThyraMIRv2 platform for indeterminate thyroid nodule risk stratification.
• To assess ThyraMIRv2's performance specifically in RAS-mutated indeterminate thyroid nodules.

Main Methods:

• The ThyraMIRv2 3-tiered microRNA classifier was evaluated on a multi-institutional cohort of Bethesda III/IV nodules.
• Positive results were defined as having a risk of malignancy ≥10%.
• Clinical utility in RAS-mutated nodules was specifically assessed.

Main Results:

• In 366 nodules, ThyraMIRv2 yielded a 30.3% positive-call rate, with higher operative and cancer diagnosis rates for ThyraMIRv2+ nodules.
• ThyraMIRv2's diagnostic parameters did not significantly improve compared to ThyGeNEXT-ThyraMIRv1.
• For 68 RAS-mutated nodules, ThyraMIRv2 showed improved sensitivity (93.8% vs 64.7%) but decreased specificity (4.5% vs 34.8%) compared to ThyGeNEXT-ThyraMIRv1.

Conclusions:

• The ThyraMIRv2 platform does not enhance indeterminate thyroid nodule malignancy stratification compared to ThyGeNEXT-ThyraMIRv1.
• ThyraMIRv2 improves malignant RAS-mutated nodule detection but increases false positives.
• Further studies with larger RAS-mutated cohorts and surgical pathology are needed to fully characterize ThyraMIRv2 performance.