title: A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells.
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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstr, 2-8, 72076, Tuebingen, Germany. dr.dr.martingrimm@googlemail.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Grimm
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmitt
authors.forename: Peter
authors.initials: P
authors.lastname: Teriete
authors.forename: Thorsten
authors.initials: T
authors.lastname: Biegner
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Muhs
authors.forename: Adelheid
authors.initials: A
authors.lastname: Munz
authors.forename: Tatjana
authors.initials: T
authors.lastname: Nadtotschi
authors.forename: Klemens
authors.initials: K
authors.lastname: König
authors.forename: Jörg
authors.initials: J
authors.lastname: Sänger
authors.forename: Oliver
authors.initials: O
authors.lastname: Feyen
authors.forename: Heiko
authors.initials: H
authors.lastname: Hofmann
authors.forename: Siegmar
authors.initials: S
authors.lastname: Reinert
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Coy
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D003850:Deoxyribonuclease I / Q000097:blood* / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D009062:Mouth Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D015999:Multivariate Analysis; D009124:Muscle Proteins / Q000097:blood* / Q000276:immunology; D009333:Neck; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D012189:Retrospective Studies; D014174:Transketolase / Q000097:blood* / Q000276:immunology; D047368:Tumor Burden
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D014408:Biomarkers, Tumor; D009124:Muscle Proteins; C505431:TKTL1 protein, human; D014174:Transketolase; C097585:DNASE1L1 protein, human; D003850:Deoxyribonuclease I