Identification of tumor antigens that elicit a humoral immune response in the sera of Chinese esophageal squamous cell carcinoma patients by modified serological proteome analysis

Cancer Lett. 2014 Mar 1;344(1):54-61. doi: 10.1016/j.canlet.2013.10.007. Epub 2013 Oct 22.

Abstract

Our aim was to identify novel tumor-associated antigens from the esophageal squamous cell carcinoma (ESCC) cell line EC0156, and related autoantibodies in sera from patients with ESCC. We used modified serological proteome analysis, involving one- and two-dimensional electrophoresis, Western blot, and MALDI-TOF/TOF-MS to identify 6 ESCC-associated antigens. From these, 105 kDa heat shock protein (HSP105) and triosephosphate isomerase (TIM) were further evaluated and we determined they could induce autoantibody responses in ESCC sera and are highly expressed in ESCC tissues. Anti-HSP105 and anti-TIM autoantibodies were found in 39.1% (18/46) and 34.8% (16/46) of patients with ESCC, respectively, but only in two controls. A receiver operating characteristic curve constructed with HSP105 and TIM gave a sensitivity of 54.3% and 95% (38/40) specificity in discriminating ESCC from matched controls. Interestingly, we found that autoantibodies against TIM in ESCC serum mainly reacted with glycosylated but not deglycosylated TIM. The preliminary results suggest the potential utility of screening autoantibodies in sera for use as biomarkers for cancer diagnosis.

Keywords: Autoantibodies; ESCC; HSP105; TAAs; TIM; mSERPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • Area Under Curve
  • Asian People
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / immunology*
  • Blotting, Western
  • Carcinoma, Squamous Cell / blood
  • Carcinoma, Squamous Cell / immunology*
  • Comet Assay
  • Electrophoresis, Gel, Two-Dimensional
  • Esophageal Neoplasms / blood
  • Esophageal Neoplasms / immunology*
  • HSP110 Heat-Shock Proteins / immunology
  • Humans
  • Immunity, Humoral / immunology
  • Immunohistochemistry
  • Proteome / immunology*
  • ROC Curve
  • Rho Guanine Nucleotide Exchange Factors / immunology
  • Sensitivity and Specificity
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • ARHGEF5 protein, human
  • Antigens, Neoplasm
  • Autoantibodies
  • Biomarkers, Tumor
  • HSP110 Heat-Shock Proteins
  • HSPH1 protein, human
  • Proteome
  • Rho Guanine Nucleotide Exchange Factors