Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer
Background The differential diagnosis between benign and malignant thyroid nodules continues to be a major challenge in clinical practice. The rising incidence of thyroid neoplasm and the low incidence of aggressive thyroid carcinoma, urges the exploration of strategies to improve the diagnostic acc...
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2025-01-01
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| author | Maria de Lurdes Godinho de Matos Mafalda Pinto Ana Gonçalves Sule Canberk Maria João Martins Bugalho Paula Soares |
| author_facet | Maria de Lurdes Godinho de Matos Mafalda Pinto Ana Gonçalves Sule Canberk Maria João Martins Bugalho Paula Soares |
| author_sort | Maria de Lurdes Godinho de Matos |
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| description | Background The differential diagnosis between benign and malignant thyroid nodules continues to be a major challenge in clinical practice. The rising incidence of thyroid neoplasm and the low incidence of aggressive thyroid carcinoma, urges the exploration of strategies to improve the diagnostic accuracy in a pre-surgical phase, particularly for indeterminate nodules, and to prevent unnecessary surgeries. Only in 2022, the 5th WHO Classification of Endocrine and Neuroendocrine Tumors, and in 2023, the 3rd Bethesda System for Reporting Thyroid Cytopathology and the European Thyroid Association included biomarkers in their guidelines. In this review, we discuss the integration of biomarkers within the routine clinical practice for diagnosis of thyroid nodules and cancer. Methodology The literature search for this review was performed through Pub Med, Science Direct, and Google Scholar. We selected 156 publications with significant contributions to this topic, with the majority (86, or 55.1%) published between January 2019 and March 2024, including some publications from our group during those periods. The inclusion criteria were based on articles published in recognized scientific journals with high contributions to the proposed topic. We excluded articles not emphasizing molecular biomarkers in refine the pre-surgical diagnosis of thyroid nodules. Results We explored genetic biomarkers, considering the division of thyroid neoplasm into BRAF-like tumor and RAS-like tumor. The specificity of BRAF mutation in the diagnosis of papillary thyroid carcinoma (PTC) is nearly 100% but its sensitivity is below 35%. RAS mutations are found in a broad spectrum of thyroid neoplasm, from benign to malignant follicular-patterned tumors, but do not increase the ability to distinguish benign from malignant lesions. The overexpression of miRNAs is correlated with tumor aggressiveness, high tumor node metastasis (TMN) stage, and recurrence, representing a real signature of thyroid cancer, particularly PTC. In addition, associations between the expression levels of selected miRNAs and the presence of specific genetic mutations have been related with aggressiveness and worse prognosis. Conclusions The knowledge of genetic and molecular biomarkers has achieved a high level of complexity, and the difficulties related to its applicability determine that their implementation in clinical practice is not yet a reality. More studies with larger series are needed to optimize their use in routine practice. Additionally, the improvement of new techniques, such as liquid biopsy and/or artificial intelligence, may be the future for a better understanding of molecular biomarkers in thyroid nodular disease. |
| format | Article |
| id | doaj-art-31f325b7e72743a2b0ce83909fbf80cd |
| institution | Kabale University |
| issn | 2167-8359 |
| language | English |
| publishDate | 2025-01-01 |
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| spelling | doaj-art-31f325b7e72743a2b0ce83909fbf80cd2025-01-22T15:05:17ZengPeerJ Inc.PeerJ2167-83592025-01-0113e1880110.7717/peerj.18801Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancerMaria de Lurdes Godinho de Matos0Mafalda Pinto1Ana Gonçalves2Sule Canberk3Maria João Martins Bugalho4Paula Soares5Department of Endocrinology, Diabetes and Metabolism, Hospital Curry Cabral, Unidade Local de Saúde São José, Centro Clínico Académico de Lisboa, Lisbon, PortugalInstituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), i3S—Institute for Research & Innovation in Health, Porto, PortugalDepartment of Pathology, Unidade Local de Saúde São João, Porto, PortugalInstituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), i3S—Institute for Research & Innovation in Health, Porto, PortugalDepartment of Endocrinology, Hospital de Santa Maria, Unidade Local de Saúde Santa Maria; Medical Faculty, University of Lisbon, Lisbon, PortugalInstituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), i3S—Institute for Research & Innovation in Health, Porto, PortugalBackground The differential diagnosis between benign and malignant thyroid nodules continues to be a major challenge in clinical practice. The rising incidence of thyroid neoplasm and the low incidence of aggressive thyroid carcinoma, urges the exploration of strategies to improve the diagnostic accuracy in a pre-surgical phase, particularly for indeterminate nodules, and to prevent unnecessary surgeries. Only in 2022, the 5th WHO Classification of Endocrine and Neuroendocrine Tumors, and in 2023, the 3rd Bethesda System for Reporting Thyroid Cytopathology and the European Thyroid Association included biomarkers in their guidelines. In this review, we discuss the integration of biomarkers within the routine clinical practice for diagnosis of thyroid nodules and cancer. Methodology The literature search for this review was performed through Pub Med, Science Direct, and Google Scholar. We selected 156 publications with significant contributions to this topic, with the majority (86, or 55.1%) published between January 2019 and March 2024, including some publications from our group during those periods. The inclusion criteria were based on articles published in recognized scientific journals with high contributions to the proposed topic. We excluded articles not emphasizing molecular biomarkers in refine the pre-surgical diagnosis of thyroid nodules. Results We explored genetic biomarkers, considering the division of thyroid neoplasm into BRAF-like tumor and RAS-like tumor. The specificity of BRAF mutation in the diagnosis of papillary thyroid carcinoma (PTC) is nearly 100% but its sensitivity is below 35%. RAS mutations are found in a broad spectrum of thyroid neoplasm, from benign to malignant follicular-patterned tumors, but do not increase the ability to distinguish benign from malignant lesions. The overexpression of miRNAs is correlated with tumor aggressiveness, high tumor node metastasis (TMN) stage, and recurrence, representing a real signature of thyroid cancer, particularly PTC. In addition, associations between the expression levels of selected miRNAs and the presence of specific genetic mutations have been related with aggressiveness and worse prognosis. Conclusions The knowledge of genetic and molecular biomarkers has achieved a high level of complexity, and the difficulties related to its applicability determine that their implementation in clinical practice is not yet a reality. More studies with larger series are needed to optimize their use in routine practice. Additionally, the improvement of new techniques, such as liquid biopsy and/or artificial intelligence, may be the future for a better understanding of molecular biomarkers in thyroid nodular disease.https://peerj.com/articles/18801.pdfGenetic and miRNAs biomarkersUltrasound fine-needle aspiration cytologyThyroid nodules and cancer5th WHO Classification of Endocrine and Neuroendocrine TumorsThe 2023 Bethesda System for Reporting Thyroid Cytopathology |
| spellingShingle | Maria de Lurdes Godinho de Matos Mafalda Pinto Ana Gonçalves Sule Canberk Maria João Martins Bugalho Paula Soares Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer PeerJ Genetic and miRNAs biomarkers Ultrasound fine-needle aspiration cytology Thyroid nodules and cancer 5th WHO Classification of Endocrine and Neuroendocrine Tumors The 2023 Bethesda System for Reporting Thyroid Cytopathology |
| title | Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer |
| title_full | Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer |
| title_fullStr | Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer |
| title_full_unstemmed | Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer |
| title_short | Insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer |
| title_sort | insights in biomarkers complexity and routine clinical practice for the diagnosis of thyroid nodules and cancer |
| topic | Genetic and miRNAs biomarkers Ultrasound fine-needle aspiration cytology Thyroid nodules and cancer 5th WHO Classification of Endocrine and Neuroendocrine Tumors The 2023 Bethesda System for Reporting Thyroid Cytopathology |
| url | https://peerj.com/articles/18801.pdf |
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