A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells

BMC Cancer. 2013 Dec 4;13:569. doi: 10.1186/1471-2407-13-569.

Abstract

Background: Biomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide molecule endonuclease DNaseX (DNaseI-like 1) has been used to identify the Apo10 protein epitope that marks tumor cells with abnormal apoptosis and proliferation. The transketolase-like protein 1 (TKTL1) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/Warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies.

Methods: Expression of Apo10 and TKTL1 was analysed retrospectively in OSCC specimen (n = 161) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo10 and TKTL1 have been used prospectively for epitope detection in monocytes (EDIM)-blood test in patients with OSCC (n = 50), breast cancer (n = 48), prostate cancer (n = 115), and blood donors/controls (n = 74).

Results: Positive Apo10 and TKTL1 expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo10 and TKTL1 expression as an independent prognostic factor for reduced tumor-specific survival. Apo10+/TKTL1+ subgroup showed the worst disease-free survival rate in OSCC.EDIM-Apo10 and EDIM-TKTL1 blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo10+/TKTL1+ led to a sensitivity of 95.8% and a specificity of 97.3% for the detection of carcinomas independent of the tumor entity.

Conclusions: The combined detection of two independent fundamental biophysical processes by the two biomarkers Apo10 and TKTL1 allows a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. Further prospective trials are warranted to validate this new concept for the diagnosis of neoplasia and tumor recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / chemistry
  • Biomarkers, Tumor / blood*
  • Carcinoma, Squamous Cell / blood*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / surgery
  • Case-Control Studies
  • Cell Line, Tumor
  • Deoxyribonuclease I / blood*
  • Deoxyribonuclease I / immunology
  • Disease-Free Survival
  • Female
  • Flow Cytometry
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Mouth Neoplasms / blood*
  • Mouth Neoplasms / mortality
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / surgery
  • Multivariate Analysis
  • Muscle Proteins / blood*
  • Muscle Proteins / immunology
  • Neck
  • Neoplasm Staging
  • Prognosis
  • ROC Curve
  • Retrospective Studies
  • Transketolase / blood*
  • Transketolase / immunology
  • Tumor Burden

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Biomarkers, Tumor
  • Muscle Proteins
  • TKTL1 protein, human
  • Transketolase
  • DNASE1L1 protein, human
  • Deoxyribonuclease I