Identifying the tumor-progressive gene expression profile in high-risk papillary thyroid cancer

Surg Today. 2021 Oct;51(10):1703-1712. doi: 10.1007/s00595-021-02262-0. Epub 2021 Mar 17.

Abstract

Purpose: Papillary thyroid cancer (PTC) is generally associated with a favorable prognosis. However, some patients have fatal disease, with locally infiltrating tumors or progressive distant metastases; yet few studies have investigated the characteristics of the tumor-progressive gene expression profile in advanced PTC. We conducted this study to clarify the gene expression status in advanced PTC and identify candidate molecules for prognostic biomarkers.

Methods: We analyzed 740 tumor-progressive gene expression levels from formalin-fixed paraffin-embedded blocks of samples from six patients with low-risk PTC and six patients with high-risk PTC, using the nCounter PanCancer Progression panel. Then, we investigated the association between the expression levels of focused genes and pathological factors in PTC patients in The Cancer Genome Atlas (TCGA) database.

Results: The expression levels of 14 genes in the high-risk PTC specimens were more than two-fold those in the low-risk PTC specimens. In the TCGA database, expression levels of four genes (CCL11, COL6A3, INHBA, and SRPX2) were significantly higher in patients with advanced PTC. Among the patients with advanced PTC, those with high SRPX2 expression levels had poor disease-free survival. Univariate and multivariate analyses revealed that high SRPX2 expression was an independent prognostic factor.

Conclusion: Based on the findings of this study, CCL11, COL6A3, INHBA, and SRPX2 are potential biomarkers that indicate advanced PTC. SRPX2, in particular, is considered a prognostic biomarker.

Keywords: CCL11; COL6A3; INHBA; Papillary thyroid cancer; SRPX2.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism*
  • Chemokine CCL11 / genetics*
  • Chemokine CCL11 / metabolism*
  • Collagen Type VI / genetics*
  • Collagen Type VI / metabolism*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Gene Expression
  • Genetic Association Studies / methods*
  • Humans
  • Inhibin-beta Subunits / genetics
  • Inhibin-beta Subunits / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology*
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Risk
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / mortality
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology
  • Transcriptome / genetics*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CCL11 protein, human
  • COL6A3 protein, human
  • Chemokine CCL11
  • Collagen Type VI
  • Membrane Proteins
  • Neoplasm Proteins
  • SRPX2 protein, human
  • inhibin beta A subunit
  • Inhibin-beta Subunits