Roles of phosphatidylinositol 3-kinase regulatory subunit alpha, activator protein-1, and programmed cell death 4 in diagnosis of papillary thyroid carcinoma

Tumour Biol. 2016 May;37(5):6519-26. doi: 10.1007/s13277-015-4476-x. Epub 2015 Dec 4.

Abstract

This study evaluated the diagnostic values of phosphatidylinositol 3-kinase regulatory subunit alpha (P85α), activator protein-1 (AP-1), and programmed cell death 4 (PDCD4) in papillary thyroid carcinoma (PTC). P85α, AP-1, and PDCD4 expressions were detected in PTC tissues (n = 116) and thyroid papillary hyperplasia (PTH) tissues (n = 90) by immunohistochemistry, western blot, and enzyme-linked immunosorbent assay (ELISA). Associations of P85α, AP-1, and PDCD4 expressions with clinicopathological features in PTC were analyzed. Diagnostic values of P85α, AP-1, and PDCD4 in PTC were evaluated by receiver operating characteristic (ROC) curve. P85α, AP-1, and PDCD4 expression levels in PTC tissues were statistically different from those in PTH tissues (all P < 0.05). In PTC tissues, AP-1 expression was positively associated with P85α expression (r = 0.841, P < 0.01), while negatively associated with PDCD4 expression (r = -0.755, P < 0.01). P85α expression was associated with lymph node metastasis (LNM) and the degree of differentiation (both P < 0.05); AP-1 and PDCD4 expressions were associated with the degree of differentiation (both P < 0.05). The diagnostic sensitivity and specificity of P85α were 92.2 and 91.1 %, respectively, with a cutoff value of 2.100 and an area under curve (AUC) of 0.966. The diagnostic sensitivity and specificity of AP-1 reached 94.4 and 93.3 % with a cutoff value of 1.655 and an AUC of 0.987. The diagnostic sensitivity and specificity of PDCD4 were 54.4 and 85.6 % with a cutoff value of 2.025 and an AUC of 0.754. P85α, AP-1, and PDCD4 proteins may be related to the tumorigenesis and progression of PTC. Moreover, P85α, AP-1, and PDCD4 proteins may serve as potential diagnostic markers to the biological behavior of PTC.

Keywords: AP-1; Diagnosis; Immunohistochemistry; P85α; PDCD4; Papillary thyroid carcinoma; ROC curve; Tumorigenesis.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis Regulatory Proteins / metabolism*
  • Biomarkers, Tumor
  • Carcinoma / diagnosis*
  • Carcinoma / metabolism*
  • Carcinoma, Papillary
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / metabolism*
  • RNA-Binding Proteins / metabolism*
  • ROC Curve
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis*
  • Thyroid Neoplasms / metabolism*
  • Transcription Factor AP-1 / metabolism*
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • PDCD4 protein, human
  • RNA-Binding Proteins
  • Transcription Factor AP-1
  • Phosphatidylinositol 3-Kinases