title: Identification of CHEK1, SLC26A4, c-KIT, TPO and TG as new biomarkers for human follicular thyroid carcinoma.
abstract: The search for preoperative biomarkers for thyroid malignancies, in particular for follicular thyroid carcinoma (FTC) diagnostics, is of utmost clinical importance. We thus aimed at screening for potential biomarker candidates for FTC. To evaluate dynamic alterations in molecular patterns as a function of thyroid malignancy progression, a comparative analysis was conducted in clinically distinct subgroups of FTC and poorly differentiated thyroid carcinoma (PDTC) nodules. NanoString analysis of FFPE samples was performed in 22 follicular adenomas, 56 FTC and 25 PDTC nodules, including oncocytic and non-oncocytic subgroups. The expression levels of CHEK1, c-KIT, SLC26A4, TG and TPO were significantly altered in all types of thyroid carcinomas. Based on collective changes of these biomarkers which correlating among each other, a predictive score has been established, allowing for discrimination between benign and FTC samples with high sensitivity and specificity. Additional transcripts related to thyroid function, cell cycle, circadian clock, and apoptosis regulation were altered in the more aggressive oncocytic subgroups only, with expression levels correlating with disease progression. Distinct molecular patterns were observed for oncocytic and non-oncocytic FTCs and PDTCs. A predictive score correlation coefficient based on collective alterations of identified here biomarkers might help to improve the preoperative diagnosis of FTC nodules.
authors.affiliation: Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Makhlouf
authors.affiliation: Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Chitikova
authors.affiliation: Division of Clinical Pathology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Pusztaszeri
authors.affiliation: Division of Clinical Pathology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Margaret
authors.initials: M
authors.lastname: Berczy
authors.affiliation: iGE3 Genomics Platform, University of Geneva, Geneva, Switzerland.
authors.forename: Celine
authors.initials: C
authors.lastname: Delucinge-Vivier
authors.affiliation: Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Frederic
authors.initials: F
authors.lastname: Triponez
authors.affiliation: Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Meyer
authors.affiliation: Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Jacques
authors.initials: J
authors.lastname: Philippe
authors.affiliation: Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Charna
authors.initials: C
authors.lastname: Dibner
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000378:metabolism*; D001324:Autoantigens / Q000032:analysis / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D000071877:Checkpoint Kinase 1 / Q000032:analysis / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006801:Humans; D007453:Iodide Peroxidase / Q000032:analysis / Q000096:biosynthesis; D033862:Iron-Binding Proteins / Q000032:analysis / Q000096:biosynthesis; D026901:Membrane Transport Proteins / Q000032:analysis / Q000096:biosynthesis; D008840:Microfilament Proteins / Q000032:analysis / Q000096:biosynthesis; D009124:Muscle Proteins / Q000032:analysis / Q000096:biosynthesis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000096:biosynthesis; D000076988:Sulfate Transporters; D013964:Thyroid Neoplasms / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D001324:Autoantigens; D014408:Biomarkers, Tumor; D033862:Iron-Binding Proteins; D026901:Membrane Transport Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; C051615:transgelin; C056658:TPO protein, human; D007453:Iodide Peroxidase; D019009:Proto-Oncogene Proteins c-kit; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1
keywords: NanoString analysis; diagnostic biomarkers; follicular thyroid carcinoma; poorly differentiated thyroid carcinoma