Prediction of novel target genes and pathways involved in tall cell variant papillary thyroid carcinoma.

Abstract:

BACKGROUND:Tall cell variant papillary thyroid carcinoma (TCPTC) is reportedly associated with aggressive clinicopathological parameters and poor outcomes; however, the molecular mechanisms underlying TCPTC remain poorly understood. METHODS:The gene mutation types and mRNA expression profiles of patients with TCPTC were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were identified. Pathways in the interaction network and the diagnostic approaches of candidate markers for TCPTC were investigated. RESULTS:BRAF mutation was particularly prevalent in TCPTC with a mutation frequency of 78%. TCPTC was associated with a patient age >45 years, tumor multifocality, extrathyroidal extension, a higher T stage, advanced AJCC TNM stages, BRAF V600E mutation, and poor disease-free survival. We identified 4138 TCPTC-related DEGs and 301 TCPTC-specific DEGs. Intriguingly, the gene expression pattern revealed that the dysregulated levels of both putative oncogenes and tumor suppressors in TCPTC were higher than those in classical/conventional variant PTC (cPTC). Functional enrichment analyses revealed that these DEGs were involved in several cancer-related pathways. A protein-protein interaction (PPI) network was constructed from the 301 TCPTC-specific DEGs, and 3 subnetworks, and 8 hub genes were verified. Receiver operating characteristic (ROC) analyses revealed that 6 hub genes, including COL5A1, COL1A1, COL10A1, COL11A1, CCL20, and CXCL5, could be used not only for the differential diagnosis of PTC from normal samples, but also for the differential diagnosis of TCPTC from cPTC samples. CONCLUSIONS:Our study might provide further insights into the investigations of the tumorigenesis mechanism of TCPTC and assists in the discovery of novel candidate diagnostic markers for TCPTC.

journal_name

Medicine (Baltimore)

journal_title

Medicine

authors

Xia F,Jiang B,Chen Y,Du X,Peng Y,Wang W,Wang Z,Li X

doi

10.1097/MD.0000000000013802

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

e13802

issue

51

eissn

0025-7974

issn

1536-5964

pii

00005792-201812210-00119

journal_volume

97

pub_type

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