Background: Significant advances have been made in detecting RNA markers that may indicate malignancy in fine needle aspiration cytology (FNAC) samples.
Objective: To review the roles of protein-coding and non-coding RNAs in differentiating between malignant and benign thyroid nodules.
Methods: A comprehensive literature search using PubMed, Science Direct, Web of Science, and SCOPUS databases was performed. We searched up until September 2024 and complemented by manual citation search.
Results: A total of 28 full-text articles were reviewed, encompassing 5770 FNAC samples, which included 3489 benign lesions and 2281 malignant lesions. The studies identified 43 messenger RNAs (mRNAs), 16 microRNAs (miRNAs), and 3 long non-coding RNAs (lncRNAs) that have the potential to distinguish malignant nodules. Among the mRNAs, PAPPA, TIMP1, and HMGA2, as well as the miRNAs, miR-146b, miR-375 and miR-222, appear to be the most promising molecules for diagnosis.
Conclusion: Numerous RNA markers have been shown to differentiate malignant from benign lesions. However, there is still a lack of patient-specific classification for thyroid cancer subtypes. Additionally, future studies should prioritize using a combination of molecular markers rather than relying on individual ones. Although current research mainly focuses on identifying cancer-specific molecules, it is important for future studies to shift towards a more patient-specific approach.
Keywords: Diagnosis; Fine-needle aspiration; Molecular marker; Thyroid cancer; lncRNAs; miRNAs.
© 2025. The Author(s).