Paving the path toward multi-omics approaches in the diagnostic challenges faced in thyroid pathology.

Introduction: Despite advancements in diagnostic methods, the classification of indeterminate thyroid nodules still poses diagnostic challenges not only in pre-surgical evaluation but even after histological evaluation of surgical specimens. Proteomics, aided by mass spectrometry and integrated with artificial intelligence and machine learning algorithms, shows great promise in identifying diagnostic markers for thyroid lesions.

Areas covered: This review provides in-depth exploration of how proteomics has contributed to the understanding of thyroid pathology. It discusses the technical advancements related to immunohistochemistry, genetic and proteomic techniques, such as mass spectrometry, which have greatly improved sensitivity and spatial resolution up to single-cell level. These improvements allowed the identification of specific protein signatures associated with different types of thyroid lesions.

Expert commentary: Among all the proteomics approaches, spatial proteomics stands out due to its unique ability to capture the spatial context of proteins in both cytological and tissue thyroid samples. The integration of multi-layers of molecular information combining spatial proteomics, genomics, immunohistochemistry or metabolomics and the implementation of artificial intelligence and machine learning approaches, represent hugely promising steps forward toward the possibility to uncover intricate relationships and interactions among various molecular components, providing a complete picture of the biological landscape whilst fostering thyroid nodule diagnosis.