The transcriptional landscape in thyroid cancer: current status of circulating biomarkers and liquid biopsy approaches.

Abstract

INTRODUCTION Thyroid cancer is the most common endocrine malignancy, and despite advances in understanding its genomic drivers, significant challenges remain in predicting tumor behavior, therapeutic response, and disease progression. This review summarizes advances in transcriptomic profiling and liquid biopsy approaches that are reshaping molecular classification, biomarker discovery, and precision management of thyroid cancer. AREAS COVERED This review examines recent advances in tissue- and liquid biopsy - based transcriptomic approaches for thyroid cancer, including bulk RNA sequencing, single-cell and spatial transcriptomics, extracellular vesicle RNAs, circulating tumor cells, and circulating non-coding RNAs, together with their applications in molecular classification, biomarker discovery, tumor heterogeneity, disease monitoring, therapeutic stratification, and precision oncology. The review also discusses emerging multi-omics integration and challenges in clinical translation. Literature was identified through systematic searches of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, supplemented by TCGA, GEO, and ClinicalTrials.gov, covering publications from January 2000 to June 2026. EXPERT OPINION Transcriptomic profiling is poised to redefine thyroid cancer management by moving beyond static morphologic classification toward biologically informed precision medicine through improved molecular classification, risk stratification, therapeutic selection, and longitudinal disease monitoring. However, routine clinical implementation will require standardized methodologies, prospective multicentre validation, and integration with liquid biopsy, multi-omics, and artificial intelligence - driven analytical frameworks.