Autoantibody against WD repeat domain 1 is a novel serological biomarker for screening of thyroid neoplasia

Clin Endocrinol (Oxf). 2013 Jul;79(1):35-42. doi: 10.1111/cen.12121. Epub 2013 May 6.

Abstract

Background: Thyroid nodules are common among adults, and accurate diagnosis is critical in for management decisions. Ultrasound and fine needle aspiration cytology are the most common methods to evaluate nodules, but they are not practical for screening large numbers of patients because of cost and time considerations.

Objective: The aim of this study was to isolate an autoantibody to tumour antigen, WD repeat domain 1 (WDR1), and evaluate its diagnostic sensitivity and specificity for thyroid neoplasms.

Patients and methods: We investigated serological biomarkers in patients with thyroid carcinoma who had a poor prognosis. Using a serological analysis of recombinant cDNA expression cloning (SEREX) strategy, we isolated WDR1 and its specific autoantibody in the sera of patients with undifferentiated thyroid carcinoma (UTC). We examined using indirect ELISA, the titre of the anti-WDR1 antibody (AWA) in 54 study patients: 10 with UTC, 20 with papillary thyroid carcinoma (PTC), 17 with benign thyroid nodule (BTN), 7 with autoimmune thyroid disease (AITD), as well as 38 controls (N).

Results: WDR1 was ubiquitously expressed in various types of thyroid tissues. However, the titre of AWA in UTC and PTC was significantly higher than that in BTN, AITD and N (P < 0·001). No significant correlation was observed between thyroid function, serum thyroglobulin and tumour diameter. The cut-off value estimated using ROC to differentiate malignancies from others was 0·95 (sensitivity 96·7%, specificity 91·9%, AUC 0·969, P < 0·001).

Conclusions: Anti-WDR1 antibody could be a novel approach for serological screening of PTC and UTC, and could be an efficient and inexpensive biomarker.

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology*
  • Blotting, Northern
  • Carcinoma / diagnosis
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Carcinoma, Papillary
  • Cell Line
  • DNA, Complementary / chemistry
  • DNA, Complementary / genetics
  • Diagnosis, Differential
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Library
  • Humans
  • Male
  • Microfilament Proteins / blood
  • Microfilament Proteins / genetics
  • Microfilament Proteins / immunology*
  • ROC Curve
  • Sequence Analysis, DNA
  • Thyroglobulin / blood
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / immunology*
  • Thyroid Nodule / diagnosis
  • Thyroid Nodule / genetics
  • Thyroid Nodule / immunology

Substances

  • Autoantibodies
  • Biomarkers, Tumor
  • DNA, Complementary
  • Microfilament Proteins
  • WDR1 protein, human
  • Thyroglobulin