Autoantibodies against TYMS and PDLIM1 proteins detected as circulatory signatures in Indian breast cancer patients

Proteomics Clin Appl. 2016 May;10(5):564-73. doi: 10.1002/prca.201500138.

Abstract

Purpose: Breast cancer (BC) is the most common invasive cancer in women worldwide. Autoantibodies (AAbs) to tumor-associated antigens (TAAs) have a great potential for the development of diagnostic biomarkers in cancer. This study was performed to identify AAbs and cognate TAAs that may improve detection of this deadly disease.

Experimental design: Serological proteome analysis of plasma samples of BC patients (N = 30) and healthy controls (N = 30) was performed to identify TAAs. Expressions of selected TAAs were also determined in breast tumor tissues (N = 10) by immunohistochemistry. An independent validation cohort (N = 124) was tested to determine diagnostic accuracy of selected AAbs titer by ELISA.

Results: Thymidylate synthase (TYMS) and C-terminal LIM domain protein 1 (PDLIM1) were found to react more specifically with plasma samples of BC patients. Both TAAs were also found to be significantly over expressed (p < 0.001) in breast tumor tissues compared to adjacent normal tissues. TYMS AAbs response was positively correlated (r = 0.778, p < 0.008) with TYMS overexpression in BC tissues. TYMS and PDLIM1 AAbs titers discriminated BC from controls with a sensitivity/specificity of 57.81%/95% and 73.44%/58.33%, respectively.

Conclusion and clinical relevance: High titers of both TYMS and PDLIM1 AAbs were significantly more prevalent in BC cases than controls. Our data recommends further investigations for evaluating their potential for BC detection.

Keywords: Autoantibodies; Autoantigens; Breast cancer; PDLIM1; TYMS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, Neoplasm / blood*
  • Antigens, Neoplasm / immunology
  • Autoantibodies / blood*
  • Autoantibodies / genetics
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / immunology
  • Breast Neoplasms / blood
  • Breast Neoplasms / diagnosis*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Early Diagnosis
  • Female
  • Humans
  • Immunohistochemistry / methods
  • India
  • LIM Domain Proteins / blood*
  • LIM Domain Proteins / immunology
  • Middle Aged
  • Sensitivity and Specificity
  • Thymidylate Synthase / blood*
  • Thymidylate Synthase / immunology
  • Transcription Factors / blood*
  • Transcription Factors / immunology
  • Transcriptome / immunology

Substances

  • Antigens, Neoplasm
  • Autoantibodies
  • Biomarkers, Tumor
  • LDB2 protein, human
  • LIM Domain Proteins
  • Transcription Factors
  • TYMS protein, human
  • Thymidylate Synthase