Key candidate genes associated with BRAFV600E in papillary thyroid carcinoma on microarray analysis

J Cell Physiol. 2019 Dec;234(12):23369-23378. doi: 10.1002/jcp.28906. Epub 2019 Jun 3.

Abstract

The mechanisms of B-type Raf kinase (BRAF) V600E mutation in papillary thyroid cancer (PTC) remain to be elucidated. With the aim to investigate the key candidate genes distinctive to BRAFV600E -PTC, we analyzed the transcriptomics data from three microarray datasets (GSE27155, GSE54958, and GSE58545) and identified 491 differentially expressed genes (DEGs) between BRAFV600E -PTC and BRAFwild type -PTC. Functional enrichment analysis of DEGs revealed that negative regulation of wound healing may be involved in the BRAFV600E -related pathogenesis in PTC. Weighted gene coexpression network analysis revealed BRAFV600E -related coexpressed genes in PTC, from which hub genes were selected. The intersection of DEGs and hub genes revealed 31 candidates, wherein GRB7, SNAP25, SLC35F2, FAM155B, HGD, and ITPR1 were rendered the key candidate genes via receiver operating characteristic curve analysis. On further characterization, the six key genes displayed significantly different expression patterns at different cytomorphology, however, with no significant difference in overall survival. These results provide novel insights into the key genes distinctive to of BRAFV600E in PTC and might be suggestive as therapeutic targets for further application.

Keywords: BRAF V600E mutation; microarray analysis; papillary thyroid carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • GRB7 Adaptor Protein / genetics
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Genetic Predisposition to Disease
  • Homogentisate 1,2-Dioxygenase / genetics
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Membrane Transport Proteins / genetics
  • Mutation*
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • Proto-Oncogene Proteins B-raf / genetics*
  • Signal Transduction
  • Synaptosomal-Associated Protein 25 / genetics
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology
  • Transcriptome*

Substances

  • Biomarkers, Tumor
  • GRB7 protein, human
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Membrane Transport Proteins
  • SLC35F2 protein, human
  • SNAP25 protein, human
  • Synaptosomal-Associated Protein 25
  • GRB7 Adaptor Protein
  • Homogentisate 1,2-Dioxygenase
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf