A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells
1 Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstr. 2-8, 72076, Tuebingen, Germany
2 German Cancer Research Center (DKFZ) Flow Cytometry Core Facility, Heidelberg, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany
3 Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
4 Department of Pathology, University Hospital Tuebingen, Liebermeisterstr. 8, 72076, Tuebingen, Germany
5 Department of Urology, University Hospital Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
6 Department of Gynecology, Clemenshospital Muenster, Duesbergweg 124, 48153, Muenster, Germany
7 Department of Anaesthesiology and Intensive Care Medicine, University Hospital Tuebingen, Hoppe-Seyler-Str. 3, 72076, Tuebingen, Germany
8 Institute of Pathology, Robert-Koch-Allee 9, 99437, Bad Berka, Germany
9 TAVARLIN AG, Reißstr. 1a, 64319, Pfungstadt, Germany
BMC Cancer 2013, 13:569 doi:10.1186/1471-2407-13-569Published: 4 December 2013
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.
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).
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.
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.