IGFBP3 as an indicator of lymph node metastasis and unfavorable prognosis for papillary thyroid carcinoma

Clin Exp Med. 2020 Nov;20(4):515-525. doi: 10.1007/s10238-020-00642-3. Epub 2020 Jun 28.

Abstract

Lymph node metastasis (LNM) is a usual event in papillary thyroid carcinoma (PTC) patients, which usually leads to poor prognosis. However, the molecular mechanisms of LNM remain unclear. Thus, we aimed to screen the possible key genes in the progression of LNM in PTC patients and further validate their roles. The study involved two phases: a discovery phase and a validation one. In the former phase, the candidate genes were screened by using bioinformatics methods. In the latter one, the genes were firstly assessed in a cohort from the cancer genome atlas (TCGA) to evaluate the associations of their expressions with clinical features and the prognostic values, and then, they were assessed at protein levels by using an immunohistochemical assay. Consequently, IGHBP3 was selected as the candidate gene, which might be enriched in several metabolism-related pathways and cancer progression-related pathways. High expressions of IGHBP3 have an association with gender, advanced clinical stages, high T stages, and the presence of LNM. Survival analysis indicated that IGHBP3 may affect the prognosis of PTC patients. The use of a tissue chip confirmed the view that IGHBP3 might play a crucial role in the LNM of PTC. In conclusion, IGHBP3 might be involved in the development of LNM in PTC patients. IGHBP3 over-expression might be a novel indicator and a potential target for PTC therapy.

Keywords: Bioinformatics method; IGHBP3; Immunohistochemistry; Papillary thyroid carcinoma; Tissue microarray.

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics*
  • Databases, Genetic
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / metabolism
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / metabolism
  • Thyroid Cancer, Papillary / mortality
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / metabolism
  • Thyroid Neoplasms / mortality
  • Thyroid Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3