Evaluation of a biomarker based blood test for monitoring surgical resection of oral squamous cell carcinomas
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The potential use of determination of biomarkers in blood for the monitoring of surgical removal of oral squamous cell carcinomas (OSCC) was evaluated using the epitope detection in monocytes (EDIM) technology.
Materials and methods
In tumor specimen, elevated Apo10 and transketolase-like 1 (TKTL1) expression was analyzed by immunohistochemistry. Apo10 and TKTL1 biomarkers have been used prospectively for EDIM blood test in patients with primary and/or recurrent OSCC (n = 92) before surgery and after curative tumor resection (n = 45).
There were highly significant (p < 0.0001) correlations found between EDIM blood scores and the tissue expression of both biomarkers measured by immunohistochemistry (Apo10: n = 89/92, 97 %; TKTL1: n = 90/92, 98 %). EDIMApo10 and EDIM-TKTL1 scores were positive in 92 % (EDIM-Apo10: n = 85/92) and 93 % (EDIM-TKTL1: n = 86/92), respectively, in patients with OSCC before surgery. The combined score EDIM-Apo10/EDIM-TKTL1 increased significantly the detection rate of tumors to 97 % (n = 89/92). After surgery, the EDIM-TKTL1 and EDIMApo10 scores significantly decreased in 75.6 and 86.7 % of the patients (p < 0.0001), respectively, in the aftercare.
The correlation of TKTL1 and Apo10 immunohistochemistry with the blood test results indicates that the EDIM blood test could serve as a non-invasive diagnostic tool (liquid biopsy) to assess surgical removal of OSCC by determination of two biomarkers.
This is the first study that has been demonstrated a reliable and successful monitoring of OSCC cancer patients by a blood test. The specific and significant decrease of EDIM-TKTL1 and EDIM-Apo10 scores after surgery could serve as a new tool for monitoring surgical removal of OSCC.
KeywordsOral squamous cell carcinoma Tumor metabolism Biomarker DNaseX Apo10 TKTL1 EDIM blood test Early detection and diagnosis
This publication was funded by the Applied Clinical Research (AKF) program of the Faculty of Medicine Tuebingen (Grant 320-0-0). The authors thank Evi Schmid, Matias Stagno, and Julia Grimm for their technical support.
Conflict of interest
The authors declare that they have no competing interests.
MG and SR conceived the study, performed the coordination, and drafted the manuscript. WK, SH, and MC carried out immunohistochemistry studies and withdrawal of blood samples. TB and AM analyzed histopathological specimen and carried out immunohistochemistry studies. PT and WK carried out the data collection and performed the statistical analyses. MK, JP, and SK performed surgical treatment and aftercare of the patients and drafted the manuscript. All authors read and approved the final manuscript.
- 3.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 Jr BW, Patton LL, Perkins D, Reid BC, Sciubba JJ, Tomar SL, Wyatt Jr AD, 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
- 5.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 PubMedCentralCrossRefPubMedGoogle Scholar
- 7.Cheng SJ, Lee JJ, Cheng SL, Chen HM, Chang HH, Wang YP, Kok SH, Kuo MY, Chiang CP (2012) Increased serum placenta growth factor level is significantly associated with progression, recurrence and poor prognosis of oral squamous cell carcinoma. Oral Oncol 48(5):424–428. doi: 10.1016/j.oraloncology.2011.12.007 CrossRefPubMedGoogle Scholar
- 9.Shukla D, Kale AD, Hallikerimath S, Yerramalla V, Subbiah V (2013) Can quantifying free-circulating DNA be a diagnostic and prognostic marker in oral epithelial dysplasia and oral squamous cell carcinoma? J Oral Maxillofac Surg Off J Am Assoc Oral Maxillofac Surg 71(2):414–418. doi: 10.1016/j.joms.2012.04.039 CrossRefGoogle Scholar
- 10.Jou YJ, Lin CD, Lai CH, Tang CH, Huang SH, Tsai MH, Chen SY, Kao JY, Lin CW (2011) Salivary zinc finger protein 510 peptide as a novel biomarker for detection of oral squamous cell carcinoma in early stages. Clin Chim Acta Int J Clin Chem 412(15-16):1357–1365. doi: 10.1016/j.cca.2011.04.004 CrossRefGoogle Scholar
- 11.St John MA, Li Y, Zhou X, Denny P, Ho CM, Montemagno C, Shi W, Qi F, Wu B, Sinha U, Jordan R, Wolinsky L, Park NH, Liu H, Abemayor E, Wong DT (2004) Interleukin 6 and interleukin 8 as potential biomarkers for oral cavity and oropharyngeal squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 130(8):929–935. doi: 10.1001/archotol.130.8.929 CrossRefPubMedGoogle Scholar
- 13.Sun W, Liu Y, Glazer CA, Shao C, Bhan S, Demokan S, Zhao M, Rudek MA, Ha PK, Califano JA (2010) TKTL1 is activated by promoter hypomethylation and contributes to head and neck squamous cell carcinoma carcinogenesis through increased aerobic glycolysis and HIF1alpha stabilization. Clin Cancer Res Off J Am Assoc Cancer Res 16(3):857–866. doi: 10.1158/1078-0432.CCR-09-2604 CrossRefGoogle Scholar
- 14.Zerilli M, Amato MC, Martorana A, Cabibi D, Coy JF, Cappello F, Pompei G, Russo A, Giordano C, Rodolico V (2008) Increased expression of transketolase-like-1 in papillary thyroid carcinomas smaller than 1.5 cm in diameter is associated with lymph-node metastases. Cancer 113(5):936–944. doi: 10.1002/cncr.23683 CrossRefPubMedGoogle Scholar
- 15.Krockenberger M, Honig A, Rieger L, Coy JF, Sutterlin M, Kapp M, Horn E, Dietl J, Kammerer U (2007) Transketolase-like 1 expression correlates with subtypes of ovarian cancer and the presence of distant metastases. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc 17(1):101–106. doi: 10.1111/j.1525-1438.2007.00799.x CrossRefGoogle Scholar
- 17.Langbein S, Zerilli M, Zur Hausen A, Staiger W, Rensch-Boschert K, Lukan N, Popa J, Ternullo MP, Steidler A, Weiss C, Grobholz R, Willeke F, Alken P, Stassi G, Schubert P, Coy JF (2006) Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted. Br J Cancer 94(4):578–585. doi: 10.1038/sj.bjc.6602962 PubMedCentralCrossRefPubMedGoogle Scholar
- 21.Schwaab J, Horisberger K, Strobel P, Bohn B, Gencer D, Kahler G, Kienle P, Post S, Wenz F, Hofmann WK, Hofheinz RD, Erben P (2011) Expression of Transketolase like gene 1 (TKTL1) predicts disease-free survival in patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy. BMC Cancer 11:363. doi: 10.1186/1471-2407-11-363 PubMedCentralCrossRefPubMedGoogle Scholar
- 23.Leers MP, Nap M, Herwig R, Delaere K, Nauwelaers F (2008) Circulating PSA-containing macrophages as a possible target for the detection of prostate cancer: a three-color/five-parameter flow cytometric study on peripheral blood samples. Am J Clin Pathol 129(4):649–656. doi: 10.1309/THWWRU8L42U5H9PB CrossRefPubMedGoogle Scholar
- 25.Herwig R, Pelzer A, Horninger W, Rehder P, Klocker H, Ramoner R, Pinggera GM, Gozzi C, Konwalinka G, Bartsch G (2004) Measurement of intracellular versus extracellular prostate-specific antigen levels in peripheral macrophages: a new approach to noninvasive diagnosis of prostate cancer. Clin Prostate Cancer 3(3):184–188CrossRefPubMedGoogle Scholar
- 30.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 PubMedCentralCrossRefPubMedGoogle Scholar
- 31.Grimm M, Cetindis M, Lehmann M, Biegner T, Munz A, Teriete P, Reinert S (2014) Apoptosis resistance-related ABCB5 and DNaseX (Apo10) expression in oral carcinogenesis. Acta Odontol Scand acceptGoogle Scholar
- 32.S3 Leitlinie Mundhöhlenkarzinom “Diagnostik und Therapie des Mundhöhlenkarzinoms” (2012) Deutsche Gesellschaft für Mund-, Kiefer- und Gesichtschirurgie AWMF-Register-Nummer 007-100OL. firstname.lastname@example.org www.leitlinienprogramm-onkologie.de
- 33.Grimm M (2012) Prognostic value of clinicopathological parameters and outcome in 484 patients with oral squamous cell carcinoma: microvascular invasion (V+) is an independent prognostic factor for OSCC. Clin Transl Oncol Offl Publ Fed Span Oncol Soc Natl Cancer Inst Mexico 14(11):870–880. doi: 10.1007/s12094-012-0867-2 Google Scholar
- 34.Billroth T (1991) General surgical pathology and therapy. Guidance for students and physicians. Lecture. Khirurgiia (Mosk) 10:136–143Google Scholar
- 37.Leon X, del Prado VM, Orus C, Lopez M, Garcia J, Quer M (2009) Influence of the persistence of tobacco and alcohol use in the appearance of second neoplasm in patients with a head and neck cancer. A case-control study. Cancer Causes Control 20(5):645–652. doi: 10.1007/s10552-008-9277-8 CrossRefPubMedGoogle Scholar
- 39.Leon X, Del Prado VM, Orus C, Kolanczak K, Garcia J, Quer M (2005) Metachronous second primary tumours in the aerodigestive tract in patients with early stage head and neck squamous cell carcinomas. Eur Arch Otorhinolaryngol Off J Eur Fed Otorhinolaryngol Soc 262(11):905–909. doi: 10.1007/s00405-005-0922-5 CrossRefGoogle Scholar
- 41.Vineis P, Alavanja M, Buffler P, Fontham E, Franceschi S, Gao YT, Gupta PC, Hackshaw A, Matos E, Samet J, Sitas F, Smith J, Stayner L, Straif K, Thun MJ, Wichmann HE, Wu AH, Zaridze D, Peto R, Doll R (2004) Tobacco and cancer: recent epidemiological evidence. J Natl Cancer Inst 96(2):99–106CrossRefPubMedGoogle Scholar
- 43.Emond JA, Pierce JP, Natarajan L, Gapuz LR, Nguyen J, Parker BA, Varki NM, Patterson RE (2014) Risk of breast cancer recurrence associated with carbohydrate intake and tissue expression of IGFI receptor. Cancer Epidemiol Biomark Prev 23(7):1273–1279. doi: 10.1158/1055-9965.EPI-13-1218 CrossRefGoogle Scholar