title: Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis.
abstract: We previously reported an upregulation of the clock transcript BMAL1, correlating with TIMP1 expression in fresh-frozen samples from papillary thyroid carcinoma (PTC). Since frozen postoperative biopsy samples are difficult to obtain, we aimed to validate the application of high-precision NanoString analysis for formalin-fixed paraffin-embedded (FFPE) thyroid nodule samples and to screen for potential biomarkers associated with PTC. No significant differences were detected between fresh-frozen and FFPE samples. NanoString analysis of 51 transcripts in 17 PTC and 17 benign nodule samples obtained from different donors and in 24 pairs of benign and PTC nodules, obtained from the same donor (multinodular goiters), confirmed significant alterations in the levels of BMAL1, c-MET, c-KIT, TIMP1, and other transcripts. Moreover, we identified for the first time alterations in CHEK1 and BCL2 levels in PTC. A predictive score was established for each sample, based on the combined expression levels of BMAL1, CHEK1, c-MET, c-KIT and TIMP1. In combination with BRAF mutation analysis, this predictive score closely correlated with the clinicopathological characteristics of the analyzed thyroid nodules. Our study identified new thyroid transcripts with altered levels in PTC using the NanoString approach. A predictive score correlation coefficient might contribute to improve the preoperative diagnosis of thyroid nodules.
authors: Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors: Zhanna
authors: Z
authors: Chitikova
authors: Division of Clinical Pathology, University Hospital of Geneva, Switzerland.
authors: Marc
authors: M
authors: Pusztaszeri
authors: Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors: Anne-Marie
authors: AM
authors: Makhlouf
authors: Division of Clinical Pathology, University Hospital of Geneva, Switzerland.
authors: Margaret
authors: M
authors: Berczy
authors: iGE3Genomics Platform, University of Geneva, Switzerland.
authors: Celine
authors: C
authors: Delucinge-Vivier
authors: Department of Thoracic and Endocrine Surgery, University Hospital of Geneva, Geneva, Switzerland.
authors: Frederic
authors: F
authors: Triponez
authors: Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospital of Geneva, Geneva, Switzerland.
authors: Patrick
authors: P
authors: Meyer
authors: 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: Jacques
authors: J
authors: Philippe
authors: 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: Charna
authors: C
authors: Dibner
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D000071877:Checkpoint Kinase 1; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D036103:Nanotechnology / Q000379:methods*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D011494:Protein Kinases / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
chemical_list: D056930:ARNTL Transcription Factors; C538960:BMAL1 protein, human; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D011494:Protein Kinases; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met; C482119:BRAF protein, human; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; D048493:Proto-Oncogene Proteins B-raf
keywords: FFPE; NanoString analysis; biomarkers; circadian clock; papillary thyroid carcinoma