Identification of new biomarkers for human papillary thyroid carcinoma employing NanoString analysis

Oncotarget. 2015 May 10;6(13):10978-93. doi: 10.18632/oncotarget.3452.

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.

Keywords: FFPE; NanoString analysis; biomarkers; circadian clock; papillary thyroid carcinoma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors / genetics
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Papillary / diagnosis*
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / surgery
  • Checkpoint Kinase 1
  • Female
  • Gene Expression Profiling*
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Nanotechnology / methods*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Paraffin Embedding
  • Prognosis
  • Protein Kinases / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • RNA, Messenger / analysis*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Gland / metabolism
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / surgery
  • Tissue Inhibitor of Metalloproteinase-1 / genetics

Substances

  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Biomarkers, Tumor
  • RNA, Messenger
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Protein Kinases
  • Proto-Oncogene Proteins c-kit
  • Proto-Oncogene Proteins c-met
  • BRAF protein, human
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • Proto-Oncogene Proteins B-raf