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Molecular Diagnostics

A review of the most promising biomarkers for early diagnosis and prognosis prediction of tongue squamous cell carcinoma

Abstract

Background

There is a great interest in developing biomarkers to enhance early detection and clinical management of tongue squamous cell carcinoma (TSCC). However, the developmental path towards a clinically valid biomarker remains extremely challenging. Ideally, the initial key step in moving a newly discovered biomarker towards clinical implementation is independent replication. Therefore, the focus of this review is on biomarkers that consistently showed clinical relevance in two or more publications.

Methods

We searched PubMed database for relevant papers across different TSCC sample sources, i.e., body fluids (saliva, serum/plasma) and tissues. No restriction regarding the date of publication was applied except for immunohistochemistry (IHC); only studies published between 2010 and June 2017 were included.

Results

The search strategy identified 1429 abstracts, of which 96 papers, examining 150 biomarkers, were eventually included. Of these papers, 66% were exploratory studies evaluating single or a panel of biomarkers in one publication. Ultimately, based on studies that had undergone validation for their clinical relevance in at least two independent studies, we identified 10 promising candidates, consisting of different types of molecules (IL-6, IL-8, and Prolactin in liquid samples; HIF-1α, SOX2, E-cadherin, vimentin, MALAT1, TP53, and NOTCH1 in tissue biopsies)

Conclusions

Although more exploratory research is needed with newer methods to identify biomarkers for TSCC, rigorous validation of biomarkers that have already shown unbiased assessment in at least two publications should be considered a high priority. Further research on these promising biomarkers or their combination in multi-institutional studies, could provide new possibilities to develop a specific panel for early diagnosis, prognosis, and individualized treatments.

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References

  1. 1.

    Vigneswaran, N. & Williams, M. D. Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral. Maxillofac. Surg. Clin. North. Am. 26, 123–141 (2014).

  2. 2.

    Mithani, S. K., Mydlarz, W. K., Grumbine, F. L., Smith, I. M. & Califano, J. A. Molecular genetics of premalignant oral lesions. Oral. Dis. 13, 126–133 (2007).

  3. 3.

    Tota, J. E. et al. Rising incidence of oral tongue cancer among white men and women in the United States, 1973-2012. Oral. Oncol. 67, 146–152 (2017).

  4. 4.

    Moore, S. R., Johnson, N. W., Pierce, A. M. & Wilson, D. F. The epidemiology of tongue cancer: a review of global incidence. Oral. Dis. 6, 75–84 (2000).

  5. 5.

    Hussein, A. A. et al. Global incidence of oral and oropharynx cancer in patients younger than 45 years versus older patients: a systematic review. Eur. J. Cancer 82, 115–127 (2017).

  6. 6.

    Brenner, H. Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet 360, 1131–1135 (2002).

  7. 7.

    Shiboski, C. H., Schmidt, B. L. & Jordan, R. C. Tongue and tonsil carcinoma: increasing trends in the U.S. population ages 20–44 years. Cancer 103, 1843–1849 (2005).

  8. 8.

    O-charoenra, P. et al. Tumour thickness predicts cervical nodal metastases and survival in early oral tongue cancer. Oral Oncol. 39, 386–390 (2003).

  9. 9.

    Klausner R. D. The Nation’s Investment in Cancer Research: A Plan and Budget Proposal for fiscal year 2003. The National Cancer Institute, Bethesda, MD, 2002.https://www.cancer.gov/about-nci/budget/about-annual-plan/nci-plan-2002.pdf

  10. 10.

    Bhatt, A. N., Mathur, R., Farooque, A., Verma, A. & Dwarakanath, B. S. Cancer biomarkers—current perspectives. Indian J. Med. Res. 132, 129–149 (2010).

  11. 11.

    Comabella, M. & Montalban, X. Body fluid biomarkers in multiple sclerosis. Lancet Neurol. 13, 113–126 (2014).

  12. 12.

    Teunissen, C. E., Malekzadeh, A., Leurs, C., Bridel, C. & Killestein, J. Body fluid biomarkers for multiple sclerosis—the long road to clinical application. Nat. Rev. Neurol. 11, 585–596 (2015).

  13. 13.

    McShane, L. M. et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br. J. Cancer 93, 387–391 (2005).

  14. 14.

    Bossuyt, P. M. et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin. Chem. 61, 1446–1452 (2015).

  15. 15.

    Oliveira, L. R. & Ribeiro-Silva, A. Prognostic significance of immunohistochemical biomarkers in oral squamous cell carcinoma. Int. J. Oral. Maxillofac. Surg. 40, 298–307 (2011).

  16. 16.

    Yu, X. & Li, Z. MicroRNA expression and its implications for diagnosis and therapy of tongue squamous cell carcinoma. J. Cell. Mol. Med. 20, 10–16 (2016).

  17. 17.

    Mordente, A., Meucci, E., Martorana, G. E. & Silvestrini, A. Cancer biomarkers discovery and validation: state of the art, problems and future perspectives. Adv. Exp. Med. Biol. 867, 9–26 (2015).

  18. 18.

    Pavlou, M. P., Diamandis, E. P. & Blasutig, I. M. The long journey of cancer biomarkers from the bench to the clinic. Clin. Chem. 59, 147–157 (2013).

  19. 19.

    Huang, X. et al. Serum proteomics study of the squamous cell carcinoma antigen 1 in tongue cancer. Oral. Oncol. 42, 26–31 (2006).

  20. 20.

    Nagler, R., Bahar, G., Shpitzer, T. & Feinmesser, R. Concomitant analysis of salivary tumor markers--a new diagnostic tool for oral cancer. Clin. Cancer Res. 12, 3979–3984 (2006).

  21. 21.

    Rai, B., Kaur, J., Jacobs, R. & Anand, S. C. Adenosine deaminase in saliva as a diagnostic marker of squamous cell carcinoma of tongue. Clin. Oral. Investig. 15, 347–349 (2011).

  22. 22.

    Suresh, A. et al. Resistance/response molecular signature for oral tongue squamous cell carcinoma. Dis. Markers 32, 51–64 (2012).

  23. 23.

    Lotfi, A. et al. Serum level of interleukin-6 in patients with oral tongue squamous cell carcinoma. Iran. J. Otorhinolaryngol. 27, 207–211 (2015).

  24. 24.

    Li, X., Qiao, Z., Long, X., Wei, J. & Cheng, Y. Serum concentration of AMDL DR-70 for the diagnosis and prognosis of carcinoma of the tongue. Br. J. Oral. Maxillofac. Surg. 43, 513–515 (2005).

  25. 25.

    Guo, X. H. et al. Decreased adiponectin level is associated with aggressive phenotype of tongue squamous cell carcinoma. Cancer Sci. 104, 206–213 (2013).

  26. 26.

    Shegefti, M. S. et al. Reduced serum levels of syndecan-1 in patients with tongue squamous cell carcinoma. Laryngoscope 126, E191–E195 (2016).

  27. 27.

    Bhatavdekar, J. M., Patel, D. D., Vora, H. H. & Balar, D. B. Circulating prolactin and TPS in monitoring the clinical course of male patients with metastatic tongue cancer: a preliminary study. Anticancer Res. 13, 237–240 (1993).

  28. 28.

    Bhatavdekar, J. M., Patel, D. D., Vora, H. H. & Balar, D. B. Circulating markers and growth factors as prognosticators in men with advanced tongue cancer. Tumour Biol. 14, 55–58 (1993).

  29. 29.

    Bhatavdekar, J. M. et al. Prolactin: its role in advanced tongue cancer. J. Surg. Oncol. 57, 115–120 (1994).

  30. 30.

    Bhatavdekar, J. M. et al. Prolactin as a local growth promoter in patients with locally advanced tongue cancer: GCRI experience. Head. Neck 22, 257–264 (2000).

  31. 31.

    Korostoff, A., Reder, L., Masood, R. & Sinha, U. K. The role of salivary cytokine biomarkers in tongue cancer invasion and mortality. Oral. Oncol. 47, 282–287 (2011).

  32. 32.

    Rivera, C., Oliveira, A. K., Costa, R. A. P., De Rossi, T. & Paes Leme, A. F. Prognostic biomarkers in oral squamous cell carcinoma: a systematic review. Oral. Oncol. 72, 38–47 (2017).

  33. 33.

    Almangush, A. et al. Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis. Br. J. Cancer 117, 856–866 (2017).

  34. 34.

    Sathyan, K. M. et al. Carcinoma of tongue and the buccal mucosa represent different biological subentities of the oral carcinoma. J. Cancer Res. Clin. Oncol. 132, 601–609 (2006).

  35. 35.

    Trivedi, T. I. et al. Identification of site-specific prognostic biomarkers in patients with oral squamous cell carcinoma. Neoplasma 58, 217–226 (2011).

  36. 36.

    Mahdey, H. M. et al. Cyclin D1 amplification in tongue and cheek squamous cell carcinoma. Asian Pac. J. Cancer Prev. 12, 2199–2204 (2011).

  37. 37.

    Ramqvist, T., Grun, N. & Dalianis, T. Human papillomavirus and tonsillar and base of tongue cancer. Viruses 7, 1332–1343 (2015).

  38. 38.

    Nakata, Y. et al. EGFR gene copy number alteration is a better prognostic indicator than protein overexpression in oral tongue squamous cell carcinomas. Eur. J. Cancer 47, 2364–2372 (2011).

  39. 39.

    Ptolemy, A. S. & Rifai, N. What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema. Scand. J. Clin. Lab. Invest. Suppl. 242, 6–14 (2010).

  40. 40.

    Hayry, V. et al. Bmi-1 expression predicts prognosis in squamous cell carcinoma of the tongue. Br. J. Cancer 102, 892–897 (2010).

  41. 41.

    Liang, Y. J. et al. Foxp3 expressed by tongue squamous cell carcinoma cells correlates with clinicopathologic features and overall survival in tongue squamous cell carcinoma patients. Oral. Oncol. 47, 566–570 (2011).

  42. 42.

    Theocharis, S. et al. RCAS1 expression in mobile tongue squamous cell carcinoma: an immunohistochemical study. Med. Sci. Monit. 17, BR228–BR234 (2011).

  43. 43.

    Theocharis, S. et al. Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival. Histopathology 59, 514–525 (2011).

  44. 44.

    Theocharis, S. et al. Histone deacetylase-1 and -2 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. J. Oral. Pathol. Med. 40, 706–714 (2011).

  45. 45.

    Zhang, J. et al. TRB3 overexpression due to endoplasmic reticulum stress inhibits AKT kinase activation of tongue squamous cell carcinoma. Oral. Oncol. 47, 934–939 (2011).

  46. 46.

    Makinen, L. K. et al. Prognostic significance of matrix metalloproteinase-2, -8, -9, and -13 in oral tongue cancer. J. Oral. Pathol. Med. 41, 394–399 (2012).

  47. 47.

    Li, H. et al. GOLPH3 overexpression correlates with tumor progression and poor prognosis in patients with clinically N0 oral tongue cancer. J. Transl. Med. 10, 168 (2012).

  48. 48.

    Theocharis, S. et al. FAK and Src expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. J. Cancer Res. Clin. Oncol. 138, 1369–1377 (2012).

  49. 49.

    Kauppila, J. H., Mattila, A. E., Karttunen, T. J. & Salo, T. Toll-like receptor 5 (TLR5) expression is a novel predictive marker for recurrence and survival in squamous cell carcinoma of the tongue. Br. J. Cancer 108, 638–643 (2013).

  50. 50.

    Ke, Z. F. et al. Expression characteristics of astrocyte elevated gene-1 (AEG-1) in tongue carcinoma and its correlation with poor prognosis. Cancer Epidemiol. 37, 179–185 (2013).

  51. 51.

    Li, Z. et al. The polycomb group protein EZH2 is a novel therapeutic target in tongue cancer. Oncotarget 4, 2532–2549 (2013).

  52. 52.

    Wen, H. et al. Decreased expression of BATF2 is significantly associated with poor prognosis in oral tongue squamous cell carcinoma. Oncol. Rep. 31, 169–174 (2014).

  53. 53.

    Li, H. et al. Prognostic significance of Flotillin1 expression in clinically N0 tongue squamous cell cancer. Int. J. Clin. Exp. Pathol. 7, 996–1003 (2014).

  54. 54.

    Theocharis, S. et al. Ephrin receptor (Eph) -A1, -A2, -A4 and -A7 expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. Pathol. Oncol. Res. 20, 277–284 (2014).

  55. 55.

    Toyoda, M. et al. Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. Br. J. Cancer 110, 2506–2513 (2014).

  56. 56.

    Ding, L. et al. alpha-smooth muscle actin-positive myofibroblasts, in association with epithelial-mesenchymal transition and lymphogenesis, is a critical prognostic parameter in patients with oral tongue squamous cell carcinoma. J. Oral. Pathol. Med. 43, 335–343 (2014).

  57. 57.

    Ramshankar, V., Soundara, V. T., Shyamsundar, V., Ramani, P. & Krishnamurthy, A. Risk stratification of early stage oral tongue cancers based on HPV status and p16 immunoexpression. Asian Pac. J. Cancer Prev. 15, 8351–8359 (2014).

  58. 58.

    Theocharis, S. et al. Extracellular signal-regulated kinase (ERK) expression and activation in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients survival. Tumour Biol. 35, 6455–6465 (2014).

  59. 59.

    Yuan, C. et al. Overexpression of metabolic markers PKM2 and LDH5 correlates with aggressive clinicopathological features and adverse patient prognosis in tongue cancer. Histopathology 65, 595–605 (2014).

  60. 60.

    Yuan, C. et al. High expression of the histone demethylase LSD1 associates with cancer cell proliferation and unfavorable prognosis in tongue cancer. J. Oral. Pathol. Med. 44, 159–165 (2015).

  61. 61.

    Zheng, G. et al. ZEB1 transcriptionally regulated carbonic anhydrase 9 mediates the chemoresistance of tongue cancer via maintaining intracellular pH. Mol. Cancer 14, 84 (2015).

  62. 62.

    Kelner, N. et al. Activin A immunoexpression as predictor of occult lymph node metastasis and overall survival in oral tongue squamous cell carcinoma. Head. Neck 37, 479–486 (2015).

  63. 63.

    Aparna, M., Rao, L., Kunhikatta, V. & Radhakrishnan, R. The role of MMP-2 and MMP-9 as prognostic markers in the early stages of tongue squamous cell carcinoma. J. Oral. Pathol. Med. 44, 345–352 (2015).

  64. 64.

    Li, H. et al. Cancer-associated fibroblasts provide a suitable microenvironment for tumor development and progression in oral tongue squamous cancer. J. Transl. Med. 13, 198 (2015).

  65. 65.

    Imayama, N. et al. FOXC2 expression is associated with tumor proliferation and invasion potential in oral tongue squamous cell carcinoma. Pathol. Oncol. Res. 21, 783–791 (2015).

  66. 66.

    Hu, F. et al. Clinicopathological features and prognostic implications of Raf kinase inhibitor protein downregulation in tongue squamous cell carcinoma. Oncol. Lett. 10, 1303–1308 (2015).

  67. 67.

    Kauppila, J. H. et al. Toll-like receptor 9 mediates invasion and predicts prognosis in squamous cell carcinoma of the mobile tongue. J. Oral. Pathol. Med. 44, 571–577 (2015).

  68. 68.

    Matsui, T., Shigeta, T., Umeda, M., & Komori, T. Vascular endothelial growth factor C (VEGF-C) expression predicts metastasis in tongue cancer. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 120, 436–442 (2015).

  69. 69.

    Naruse, T. et al. Immunohistochemical study of vascular endothelial growth factor-C/vascular endothelial growth factor receptor-3 expression in oral tongue squamous cell carcinoma: correlation with the induction of lymphangiogenesis. Oncol. Lett. 10, 2027–2034 (2015).

  70. 70.

    Theocharis, S. et al. Evaluation of cannabinoid CB1 and CB2 receptors expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patients’ survival. Tumour Biol. 37, 3647–3656 (2016).

  71. 71.

    Al-Shareef, H. et al. Use of NRP1, a novel biomarker, along with VEGF-C, VEGFR-3, CCR7 and SEMA3E, to predict lymph node metastasis in squamous cell carcinoma of the tongue. Oncol. Rep. 36, 2444–2454 (2016).

  72. 72.

    Heikkinen, I. et al. Does securin expression have significance in prognostication of oral tongue cancer? A pilot study. Eur. Arch. Otorhinolaryngol. 273, 3905–3911 (2016).

  73. 73.

    Zhao, X. P. et al. Overexpression of HMGA2 promotes tongue cancer metastasis through EMT pathway. J. Transl. Med. 14, 26 (2016).

  74. 74.

    Wang, W. et al. Hexokinase 2 enhances the metastatic potential of tongue squamous cell carcinoma via the SOD2-H2O2 pathway. Oncotarget 8, 3344–3354 (2017).

  75. 75.

    Hu, H. et al. Overexpression of suppressor of zest 12 is associated with cervical node metastasis and unfavorable prognosis in tongue squamous cell carcinoma. Cancer Cell. Int. 17, 26 (2017).

  76. 76.

    Theocharis, S. et al. Phosphorylated epidermal growth factor receptor expression is associated with clinicopathologic parameters and patient survival in mobile tongue squamous cell carcinoma. J. Oral. Maxillofac. Surg. 75, 632–640 (2017).

  77. 77.

    Lindell Jonsson, E., Nylander, K., Hallen, L. & Laurell, G. Immunohistochemical analysis of EGFR and hyaluronan in tongue cancer and the development of regional recurrence in patients initially diagnosed N0. Acta Otolaryngol. 137, 877–882 (2017).

  78. 78.

    Ong, H. S. et al. Cytoplasmic neuropilin 2 is associated with metastasis and a poor prognosis in early tongue cancer patients. Int. J. Oral. Maxillofac. Surg. 46, 1205–1219 (2017).

  79. 79.

    Sakamoto, K. et al. Overexpression of SIP1 and downregulation of E-cadherin predict delayed neck metastasis in stage I/II oral tongue squamous cell carcinoma after partial glossectomy. Ann. Surg. Oncol. 19, 612–619 (2012).

  80. 80.

    Wang, C. et al. Deregulation of Snai2 is associated with metastasis and poor prognosis in tongue squamous cell carcinoma. Int. J. Cancer 130, 2249–2258 (2012).

  81. 81.

    Albert, S. et al. Prognostic value of the chemokine receptor CXCR4 and epithelial-to-mesenchymal transition in patients with squamous cell carcinoma of the mobile tongue. Oral. Oncol. 48, 1263–1271 (2012).

  82. 82.

    Liu, P. F. et al. Vimentin is a potential prognostic factor for tongue squamous cell carcinoma among five epithelial-mesenchymal transition-related proteins. PLoS ONE 12, e0178581 (2017).

  83. 83.

    Liang, X. et al. Hypoxia-inducible factor-1 alpha, in association with TWIST2 and SNIP1, is a critical prognostic factor in patients with tongue squamous cell carcinoma. Oral. Oncol. 47, 92–97 (2011).

  84. 84.

    Huang, C. et al. Association of increased ligand cyclophilin A and receptor CD147 with hypoxia, angiogenesis, metastasis and prognosis of tongue squamous cell carcinoma. Histopathology 60, 793–803 (2012).

  85. 85.

    Han, M. W. et al. Role of FDG-PET as a biological marker for predicting the hypoxic status of tongue cancer. Head. Neck 34, 1395–1402 (2012).

  86. 86.

    Kang, F. W., Gao, Y., Que, L., Sun, J. & Wang, Z. L. Hypoxia-inducible factor-1alpha overexpression indicates poor clinical outcomes in tongue squamous cell carcinoma. Exp. Ther. Med. 5, 112–118 (2013).

  87. 87.

    Du, L. et al. Sox2 nuclear expression is closely associated with poor prognosis in patients with histologically node-negative oral tongue squamous cell carcinoma. Oral. Oncol. 47, 709–713 (2011).

  88. 88.

    Huang, C. F., Xu, X. R., Wu, T. F., Sun, Z. J. & Zhang, W. F. Correlation of ALDH1, CD44, OCT4 and SOX2 in tongue squamous cell carcinoma and their association with disease progression and prognosis. J. Oral. Pathol. Med. 43, 492–498 (2014).

  89. 89.

    Fang, Z. et al. Increased expression of the long non-coding RNA UCA1 in tongue squamous cell carcinomas: a possible correlation with cancer metastasis. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 117, 89–95 (2014).

  90. 90.

    Gao, W., Chan, J. Y. & Wong, T. S. Long non-coding RNA deregulation in tongue squamous cell carcinoma. Biomed. Res. Int. 2014, 405860 (2014).

  91. 91.

    Jia, L. F. et al. Expression, regulation and roles of miR-26a and MEG3 in tongue squamous cell carcinoma. Int. J. Cancer 135, 2282–2293 (2014).

  92. 92.

    Zhang, H. et al. Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma. Tumour Biol. 36, 8805–8809 (2015).

  93. 93.

    Huang, W. et al. Long non-coding RNA NKILA inhibits migration and invasion of tongue squamous cell carcinoma cells via suppressing epithelial-mesenchymal transition. Oncotarget 7, 62520–62532 (2016).

  94. 94.

    Li, Z. Q., Zou, R., Ouyang, K. X. & Ai, W. J. An in vitro study of the long non-coding RNA TUG1 in tongue squamous cell carcinoma. J. Oral. Pathol. Med. 46, 956–960 (2017).

  95. 95.

    Ouyang, K. X. et al. TUC338 overexpression leads to enhanced proliferation and reduced apoptosis in tongue squamous cell carcinoma cells in vitro. J. Oral. Maxillofac. Surg. 75, 423–428 (2017).

  96. 96.

    Yu, J. et al. Upregulated long non-coding RNA LINC00152 expression is associated with progression and poor prognosis of tongue squamous cell carcinoma. J. Cancer 8, 523–530 (2017).

  97. 97.

    Yu, J. et al. Overexpression long non-coding RNA LINC00673 is associated with poor prognosis and promotes invasion and metastasis in tongue squamous cell carcinoma. Oncotarget 8, 16621–16632 (2017).

  98. 98.

    Fang, Z. et al. Long non-coding RNA MALAT-1 modulates metastatic potential of tongue squamous cell carcinomas partially through the regulation of small proline rich proteins. BMC Cancer 16, 706 (2016).

  99. 99.

    Zhang, T. H. et al. Long non-coding RNA MALAT1 interacts with miR-124 and modulates tongue cancer growth by targeting JAG1. Oncol. Rep. 37, 2087–2094 (2017).

  100. 100.

    Hartig, G. et al. Fluorescent in situ hybridizaton evaluation of p53 gene deletions at a tumor interface of lingual carcinoma. Laryngoscope 110, 1474–1478 (2000).

  101. 101.

    Fujii, M., Ishiguro, R., Yamashita, T. & Tashiro, M. Cyclin D1 amplification correlates with early recurrence of squamous cell carcinoma of the tongue. Cancer Lett. 172, 187–192 (2001).

  102. 102.

    Goto, H., Kawano, K., Kobayashi, I., Sakai, H. & Yanagisawa, S. Expression of cyclin D1 and GSK-3beta and their predictive value of prognosis in squamous cell carcinomas of the tongue. Oral. Oncol. 38, 549–556 (2002).

  103. 103.

    Hannen, E. J. et al. Different chromosomal imbalances in metastasized and nonmetastasized tongue carcinomas identified by comparative genomic hybridization. Oral. Oncol. 40, 364–371 (2004).

  104. 104.

    Shimizu, Y., Kondo, S., Shirai, A., Furukawa, M. & Yoshizaki, T. A single nucleotide polymorphism in the matrix metalloproteinase-1 and interleukin-8 gene promoter predicts poor prognosis in tongue cancer. Auris Nasus Larynx 35, 381–389 (2008).

  105. 105.

    Angiero, F. et al. Comparative analysis of c-erbB-2 (HER-2/neu) in squamous cell carcinoma of the tongue: does over-expression exist? And what is its correlation with traditional diagnostic parameters? J. Oral. Pathol. Med. 37, 145–150 (2008).

  106. 106.

    Ryott, M. et al. EGFR protein overexpression and gene copy number increases in oral tongue squamous cell carcinoma. Eur. J. Cancer 45, 1700–1708 (2009).

  107. 107.

    Prapinjumrune, C. et al. DNA amplification and expression of FADD in oral squamous cell carcinoma. J. Oral. Pathol. Med. 39, 525–532 (2010).

  108. 108.

    Aida, J. et al. Telomere lengths in the oral epithelia with and without carcinoma. Eur. J. Cancer 46, 430–438 (2010).

  109. 109.

    Supic, G., Kozomara, R., Jovic, N., Zeljic, K. & Magic, Z. Hypermethylation of RUNX3 but not WIF1 gene and its association with stage and nodal status of tongue cancers. Oral. Dis. 17, 794–800 (2011).

  110. 110.

    Young, R. J. et al. Frequency of fibroblast growth factor receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome. Oral. Oncol. 49, 576–581 (2013).

  111. 111.

    Mostaan, L. V. et al. Survivin gene polymorphism association with tongue squamous cell carcinoma. Genet. Test. Mol. Biomark. 17, 74–77 (2013).

  112. 112.

    Adduri, R. S. et al. TP53 Pro72 allele is enriched in oral tongue cancer and frequently mutated in esophageal cancer in India. PLoS ONE 9, e114002 (2014).

  113. 113.

    Tan, D. S. et al. Tongue carcinoma infrequently harbor common actionable genetic alterations. BMC Cancer 14, 679 (2014).

  114. 114.

    Lim, A. M. et al. Differential mechanisms of CDKN2A (p16) alteration in oral tongue squamous cell carcinomas and correlation with patient outcome. Int. J. Cancer 135, 887–895 (2014).

  115. 115.

    Morita, T. et al. Characterizing genetic transitions of copy number alterations and allelic imbalances in oral tongue carcinoma metastasis. Genes Chromosomes Cancer 55, 975–986 (2016).

  116. 116.

    Kakuya, T. et al. Prognostic significance of gene amplification of ACTN4 in stage I and II oral tongue cancer. Int. J. Oral. Maxillofac. Surg. 46, 968–976 (2017).

  117. 117.

    Atula, S., Kurvinen, K., Grenman, R. & Syrjanen, S. SSCP pattern indicative for p53 mutation is related to advanced stage and high-grade of tongue cancer. Eur. J. Cancer B. Oral. Oncol. 32B, 222–229 (1996).

  118. 118.

    Heaton, C. M., Durr, M. L., Tetsu, O., van Zante, A. & Wang, S. J. TP53 and CDKN2a mutations in never-smoker oral tongue squamous cell carcinoma. Laryngoscope 124, E267–E273 (2014).

  119. 119.

    Adduri, R. et al. P53 nuclear stabilization is associated with FHIT loss and younger age of onset in squamous cell carcinoma of oral tongue. BMC Clin. Pathol. 14, 37 (2014).

  120. 120.

    Krishnan, N. et al. Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence. F1000Res. 4, 1215 (2015).

  121. 121.

    Vettore, A. L. et al. Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance. Genome Med. 7, 98 (2015).

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Author information

Conception and design: T.F., J.D.V., and M.N.H.; data acquisition: A.A.H.; quality assessment: A.A.H. and M.N.H.; analysis and interpretation of the data: A.A.H. and M.N.H.; manuscript preparation: A.A.H. and M.N.H.; manuscript editing: E.B., T.F., and J.D.V.; and manuscript reviewing: R.H.B., C.R.L., and E.B.

Competing interests

The authors declare no competing interests.

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This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Correspondence to Marco N. Helder.

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