title: Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies.
abstract: BACKGROUND
  One of the common malignant tumors of the head and neck worldwide with generally unfavorable prognosis is squamous cell carcinoma (OSCC) of the oral cavity. Early detection of primary, secondary, or recurrent OSCC by liquid biopsy tools is much needed.
  
  
  METHODS
  Twelve blood biomarkers were used for monitoring a case of OSCC suffering from precancerous oral lichen ruber planus mucosae (OLP). After curative R0 tumor resection of primary OSCC (buccal mucosa), elevated epitope detection in monocytes (EDIM)-Apo10, EDIM-transketolase-like-1 (TKTL1), squamous cell carcinoma antigen (SCC-Ag), total serum lactate dehydrogenase (LDH), and its anaerobic isoforms (LDH-4, LDH-5) decreased to normal levels. Three and six months after surgery, transformation of suspicious mucosal lesions has been accompanied with an increase of EDIM scores, total serum LDH values, and a metabolic shift from aerobic (decrease of LDH-1, LDH-2) to anaerobic (increase of LDH-4, LDH-5) conditions. Two months later, secondary OSCC was histopathologically analyzed after tissue biopsy. Cytokeratin fraction 21-1 (CYFRA 21-1), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) were not affected during the clinical course of carcinogenesis.
  
  
  CONCLUSIONS
  A combination strategy using a standardized panel of established (metabolic) blood biomarkers (TKTL1, LDH, LDH isoenzymes) is worth and can be recommended among others (apoptosis resistance-related Apo10, SCC-Ag) for early detection and diagnosis of primary, secondary, and recurrent OSCC. A tandem strategy utilizing (metabolic pronounced) routine liquid biopsies with imaging techniques may enhance diagnosis of OSCC in the future. Although we demonstrated the diagnostic utility of separated liquid biopsies in our previous study cohorts, further investigations in a larger patient cohort are necessary to recommend this combination strategy (EDIM blood test, LDH value, metabolic shift of LDH isoenzymes, and others, e.g., SCC-Ag or immunophenotyping) as a diagnostic tool for the addition to the OSCC staging system and as a routine procedure in the aftercare.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tuebingen University Hospital, Osianderstrasse 2-8, 72076, Tuebingen, Germany. dr.dr.martingrimm@googlemail.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Grimm
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tuebingen University Hospital, Osianderstrasse 2-8, 72076, Tuebingen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoefert
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tuebingen University Hospital, Osianderstrasse 2-8, 72076, Tuebingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Krimmel
authors.affiliation: Department of Pathology, University Hospital Tuebingen, Liebermeisterstrasse 8, 72076, Tuebingen, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Biegner
authors.affiliation: Zyagnum AG, Lyoner Straße 20, 60528, Frankfurt am Main, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Feyen
authors.affiliation: Cancer Research Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Teriete
authors.affiliation: Department of Oral and Maxillofacial Surgery, Tuebingen University Hospital, Osianderstrasse 2-8, 72076, Tuebingen, Germany.
authors.forename: Siegmar
authors.initials: S
authors.lastname: Reinert
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D001706:Biopsy / Q000379:methods; D063646:Carcinogenesis / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017676:Lichen Planus, Oral / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D037981:Neck Dissection; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000473:pathology; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarkers; Cytokeratin fraction 21-1; Epitope detection in monocytes (EDIM) technology; Lactate dehydrogenase; Oral squamous cell carcinoma; Squamous cell carcinoma antigen; Transketolase-like-1; monitoring