Monitoring carcinogenesis in a case of oral squamous cell carcinoma using a panel of new metabolic blood biomarkers as liquid biopsies
- 443 Downloads
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.
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.
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.
KeywordsBiomarkers monitoring Transketolase-like-1 Lactate dehydrogenase Squamous cell carcinoma antigen Cytokeratin fraction 21-1 Epitope detection in monocytes (EDIM) technology Oral squamous cell carcinoma
oral squamous cell carcinoma
epitope detection in monocytes
squamous cell carcinoma antigen
- CYFRA 21-1
cyotokeratin fraction 21–-1
Hematoxylin and Eosin
We thank biovis’ Diagnostik MVZ especially Melanie Hügen and Martina Thümmler for the technical support.
MG, SH, and MK performed follow-up of the patient and were major contributors in conducting, writing, and revising the manuscript. TB and MG evaluated the immunohistology and immunohistochemistry slides. OF performed the flow cytometric analysis. PT and SR conceived the study and drafted the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Written informed consent to participate was obtained prospectively from the patient (Ethics Committee Tuebingen, Germany, approval number: 562-2013BO2).
OF is an employee and shareholder of Zyagnum AG, Frankfurt am Main, Germany, and declares a potential conflict of interest due to the possible utilization of Apo10 and TKTL1 for diagnostic and/or therapeutic purposes. The authors have no other affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
- 1.Rethman MP, Carpenter W, Cohen EE, Epstein J, Evans CA, Flaitz CM, Graham FJ, Hujoel PP, Kalmar JR, Koch WM, Lambert PM, Lingen MW, Oettmeier BW, Jr., Patton LL, Perkins D, Reid BC, Sciubba JJ, Tomar SL, Wyatt AD, Jr., Aravamudhan K, Frantsve-Hawley J, Cleveland JL, Meyer DM, American Dental Association Council on Scientific Affairs Expert Panel on Screening for Oral Souamous Cell C (2012) Evidence-based clinical recommendations regarding screening for oral squamous cell carcinomas. Tex Dent J 129 (5):491–507PubMedGoogle Scholar
- 6.Krimmel M, Hoffmann J, Krimmel C, Cornelius CP, Schwenzer N (1998) Relevance of SCC-Ag, CEA, CA 19.9 and CA 125 for diagnosis and follow-up in oral cancer. J Craniomaxillofac Surg Off Publ European Assoc Craniomaxillofac Surg 26(4):243–248Google Scholar
- 8.Grimm M, Cetindis M, Lehmann M, Biegner T, Munz A, Teriete P, Kraut W, Reinert S (2014) Association of cancer metabolism-related proteins with oral carcinogenesis—indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma? J Transl Med 12:208. doi: 10.1186/1479-5876-12-208 CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Grimm M, Krimmel M, Hoefert S, Kraut W, Calgeer B, Biegner T, Teriete P, Munz A, Reinert S (2015) Monitoring a ‘metabolic shift’ after surgical resection of oral squamous cell carcinomas by serum lactate dehydrogenase. J Oral Pathol Med Off Publ Int Assoc Oral Pathologists Am Acad Oral Pathol. doi: 10.1111/jop.12374 Google Scholar
- 12.Garbe C, Peris K, Hauschild A, Saiag P, Middleton M, Spatz A, Grob JJ, Malvehy J, Newton-Bishop J, Stratigos A, Pehamberger H, Eggermont AM, European Dermatology F, European Association of D-O, European Organization of R, Treatment of C (2012) Diagnosis and treatment of melanoma. European consensus-based interdisciplinary guideline–Update 2012. Eur J Cancer 48(15):2375–2390. doi: 10.1016/j.ejca.2012.06.013 CrossRefPubMedGoogle Scholar
- 13.Grimm M, Schmitt S, Teriete P, Biegner T, Stenzl A, Hennenlotter J, Muhs HJ, Munz A, Nadtotschi T, Konig K, Sanger J, Feyen O, Hofmann H, Reinert S, Coy JF (2013) A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells. BMC Cancer 13(1):569. doi: 10.1186/1471-2407-13-569 CrossRefPubMedPubMedCentralGoogle Scholar
- 25.Kostakoglu L, Fardanesh R, Posner M, Som P, Rao S, Park E, Doucette J, Stein EG, Gupta V, Misiukiewicz K, Genden E (2013) Early detection of recurrent disease by FDG-PET/CT leads to management changes in patients with squamous cell cancer of the head and neck. Oncologist 18(10):1108–1117. doi: 10.1634/theoncologist.2013-0068 CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Suenaga Y, Kitajima K, Ishihara T, Sasaki R, Otsuki N, Nibu KI, Minamikawa T, Kiyota N, Sugimura K (2015) FDG-PET/contrast-enhanced CT as a post-treatment tool in head and neck squamous cell carcinoma: comparison with FDG-PET/non-contrast-enhanced CT and contrast-enhanced CT. European Radiol. doi: 10.1007/s00330-015-3902-1 Google Scholar
- 27.Yeh CY, Lin CL, Chang MC, Chen HM, Kok SH, Chang SH, Kuo YS, Hahn LJ, Chan CP, Lee JJ, Jeng JH (2015) Differences in oral habit and lymphocyte subpopulation affect malignant transformation of patients with oral precancer. J Formos Med Assoc Taiwan yi zhi. doi: 10.1016/j.jfma.2015.07.017 Google Scholar
- 31.Young M (2014) Immunological phenotypes of premalignant oral lesions and the immune shifts with the development of head and neck cancer. Austin J Otolaryngol 1(2):7Google Scholar
- 36.Weigum SE, Floriano PN, Redding SW, Yeh CK, Westbrook SD, McGuff HS, Lin A, Miller FR, Villarreal F, Rowan SD, Vigneswaran N, Williams MD, McDevitt JT (2010) Nano-bio-chip sensor platform for examination of oral exfoliative cytology. Cancer Prev Res 3(4):518–528. doi: 10.1158/1940-6207.CAPR-09-0139 CrossRefGoogle Scholar