Abstract
Aim
The aim of this study was to define TAC1 and TACR1 methylation profiles for head and neck squamous cell carcinoma (HNSCC) tumors at diagnosis and follow-up and to evaluate their prognostic significance and value as a biomarker of recurrence.
Materials and methods
TAC1 and TACR1 expression was measured in a panel of cell lines by quantitative RT-PCR. The TAC1 and TACR1 promoter methylation status was determined by quantitative methylation-specific PCR.
Results
Methylation was associated with TAC1 and TACR1 transcription inhibition. TAC1 methylation in 49/100 (49 %) of HNSCC tumor specimens significantly correlated with p16 methylation (P = 0.010), E-cadherin methylation (P = 0.041), galanin methylation (P = 0.037), and disease-free survival (P = 0.002). Stage III and IV patients manifesting TAC1 hypermethylation had significantly shorter survivals than did patients without TAC1 methylation (P = 0.022). TACR1 methylation in 34/100 (34 %) cases was significantly correlated with galanin methylation (P = 0.014) and GALR1 methylation (P = 0.004). TAC1 promoter hypermethylation was statistically correlated with reduced disease-free survival (log-rank test, P = 0.002). In multivariate logistic-regression analysis, methylation of TAC1 and of the gene pair TAC1 and TACR1 was associated with an odds ratio for recurrence of 3.35 (95 % CI, 1.37–8.19; P = 0.008) and 5.09 (95 % CI, 1.44–18.02; P = 0.011), respectively.
Conclusion
CpG hypermethylation is a likely mechanism of TAC1 and TACR1 gene inactivation, supporting the hypothesis that TAC1 and TACR1 play a role in the tumorigenesis of HNSCC and that this hypermethylation may serve as an important biomarker.
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References
Barreto SG, Carati CJ, Schloithe AC, Toouli J, Saccone GT (2010) The combination of neurokinin-1 and galanin receptor antagonists ameliorates caerulein-induced acute pancreatitis in mice. Peptides 31(2):315–321. doi:10.1016/j.peptides.2009.11.014
Bolden JE, Peart MJ, Johnstone RW (2006) Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov 5(9):769–784. doi:10.1038/nrd2133
Brenner JC, Graham MP, Kumar B, Saunders LM, Kupfer R, Lyons RH, Bradford CR, Carey TE (2010) Genotyping of 73 UM-SCC head and neck squamous cell carcinoma cell lines. Head Neck 32(4):417–426. doi:10.1002/hed.21198
Carvalho AL, Henrique R, Jeronimo C, Nayak CS, Reddy AN, Hoque MO, Chang S, Brait M, Jiang WW, Kim MM, Claybourne Q, Goldenberg D, Khan Z, Khan T, Westra WH, Sidransky D, Koch W, Califano JA (2011) Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance. Clin Cancer Res 17(14):4782–4789. doi:10.1158/1078-0432.CCR-11-0324
David S, Kan T, Cheng Y, Agarwal R, Jin Z, Mori Y (2009) Aberrant silencing of the endocrine peptide gene tachykinin-1 in gastric cancer. Biochem Biophys Res Commun 378(3):605–609. doi:10.1016/j.bbrc.2008.11.078
Esteller M (2008) Epigenetics in cancer. N Engl J Med 358(11):1148–1159. doi:10.1056/NEJMra072067
Forastiere A, Koch W, Trotti A, Sidransky D (2001) Head and neck cancer. N Engl J Med 345(26):1890–1900. doi:10.1056/NEJMra001375
Holmes A, Heilig M, Rupniak NM, Steckler T, Griebel G (2003) Neuropeptide systems as novel therapeutic targets for depression and anxiety disorders. Trends Pharmacol Sci 24(11):580–588. doi:10.1016/j.tips.2003.09.011
Jaafari N, Hua G, Adelaide J, Jule Y, Imbert J (2008) Expression of the tachykinin receptor mRNAs in healthy human colon. Eur J Pharmacol 599(1–3):121–125. doi:10.1016/j.ejphar.2008.09.024
Jeschke J, Van Neste L, Glockner SC, Dhir M, Calmon MF, Deregowski V, Van Criekinge W, Vlassenbroeck I, Koch A, Chan TA, Cope L, Hooker CM, Schuebel KE, Gabrielson E, Winterpacht A, Baylin SB, Herman JG, Ahuja N (2012) Biomarkers for detection and prognosis of breast cancer identified by a functional hypermethylome screen. Epigenetics 7(7):701–709. doi:10.4161/epi.20445
Jin Z, Olaru A, Yang J, Sato F, Cheng Y, Kan T, Mori Y, Mantzur C, Paun B, Hamilton JP, Ito T, Wang S, David S, Agarwal R, Beer DG, Abraham JM, Meltzer SJ (2007) Hypermethylation of tachykinin-1 is a potential biomarker in human esophageal cancer. Clin Cancer Res 13(21):6293–6300. doi:10.1158/1078-0432.CCR-07-0818
Jin Z, Cheng Y, Olaru A, Kan T, Yang J, Paun B, Ito T, Hamilton JP, David S, Agarwal R, Selaru FM, Sato F, Abraham JM, Beer DG, Mori Y, Shimada Y, Meltzer SJ (2008) Promoter hypermethylation of CDH13 is a common, early event in human esophageal adenocarcinogenesis and correlates with clinical risk factors. Int J Cancer 123(10):2331–2336. doi:10.1002/ijc.23804
Kanazawa T, Iwashita T, Kommareddi P, Nair T, Misawa K, Misawa Y, Ueda Y, Tono T, Carey TE (2007) Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors. Oncogene 26(39):5762–5771. doi:10.1038/sj.onc.1210384
Kanazawa T, Kommareddi PK, Iwashita T, Kumar B, Misawa K, Misawa Y, Jang I, Nair TS, Iino Y, Carey TE (2009) Galanin receptor subtype 2 suppresses cell proliferation and induces apoptosis in p53 mutant head and neck cancer cells. Clin Cancer Res 15(7):2222–2230. doi:10.1158/1078-0432.CCR-08-2443
Kanazawa T, Misawa K, Carey TE (2010) Galanin receptor subtypes 1 and 2 as therapeutic targets in head and neck squamous cell carcinoma. Expert Opin Ther Targets 14(3):289–302. doi:10.1517/14728221003598922
Katz MH (2011) Multivariable analysis: a practical guide for clinicians and public health researchers. Setting up a multivariable analysis. Cambridge University Press, Cambridge
Koon HW, Zhao D, Na X, Moyer MP, Pothoulakis C (2004) Metalloproteinases and transforming growth factor-alpha mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes. J Biol Chem 279(44):45519–45527. doi:10.1074/jbc.M408523200
Kumar B, Cordell KG, Lee JS, Worden FP, Prince ME, Tran HH, Wolf GT, Urba SG, Chepeha DB, Teknos TN, Eisbruch A, Tsien CI, Taylor JM, D’Silva NJ, Yang K, Kurnit DM, Bauer JA, Bradford CR, Carey TE (2008) EGFR, p16, HPV Titer, Bcl-xL and p53, sex, and smoking as indicators of response to therapy and survival in oropharyngeal cancer. J Clin Oncol 26(19):3128–3137. doi:10.1200/JCO.2007.12.7662
Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Mori M, Croce CM (2003) Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res 63(13):3724–3728
Lappano R, Maggiolini M (2011) G protein-coupled receptors: novel targets for drug discovery in cancer. Nat Rev Drug Discov 10(1):47–60. doi:10.1038/nrd3320
Lieb K, Fiebich BL, Berger M, Bauer J, Schulze-Osthoff K (1997) The neuropeptide substance P activates transcription factor NF-kappa B and kappa B-dependent gene expression in human astrocytoma cells. J Immunol 159(10):4952–4958
Misawa K, Ueda Y, Kanazawa T, Misawa Y, Jang I, Brenner JC, Ogawa T, Takebayashi S, Grenman RA, Herman JG, Mineta H, Carey TE (2008) Epigenetic inactivation of galanin receptor 1 in head and neck cancer. Clin Cancer Res 14(23):7604–7613. doi:10.1158/1078-0432.CCR-07-4673
Misawa K, Kanazawa T, Misawa Y, Imai A, Endo S, Hakamada K, Mineta H (2011) Hypermethylation of collagen alpha2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer. Cancer Biomarkers Sect A Disease Markers 10(3–4):135–144. doi:10.3233/CBM-2012-0242
Mori Y, Cai K, Cheng Y, Wang S, Paun B, Hamilton JP, Jin Z, Sato F, Berki AT, Kan T, Ito T, Mantzur C, Abraham JM, Meltzer SJ (2006) A genome-wide search identifies epigenetic silencing of somatostatin, tachykinin-1, and 5 other genes in colon cancer. Gastroenterology 131(3):797–808. doi:10.1053/j.gastro.2006.06.006
Ovchinnikov DA, Cooper MA, Pandit P, Coman WB, Cooper-White JJ, Keith P, Wolvetang EJ, Slowey PD, Punyadeera C (2012) Tumor-suppressor gene promoter hypermethylation in Saliva of head and neck cancer patients. Transl Oncol 5(5):321–326
Park HL, Kim MS, Yamashita K, Westra W, Carvalho AL, Lee J, Jiang WW, Baek JH, Liu J, Osada M, Moon CS, Califano JA, Mori M, Sidransky D (2008) DCC promoter hypermethylation in esophageal squamous cell carcinoma. Int J Cancer 122(11):2498–2502. doi:10.1002/ijc.23434
Park CK, Kim JE, Kim JY, Song SW, Kim JW, Choi SH, Kim TM, Lee SH, Kim IH, Park SH (2012) The changes in MGMT promoter methylation status in initial and recurrent glioblastomas. Transl Oncol 5(5):393–397
Pennefather JN, Lecci A, Candenas ML, Patak E, Pinto FM, Maggi CA (2004) Tachykinins and tachykinin receptors: a growing family. Life Sci 74(12):1445–1463
Pinto FM, Almeida TA, Hernandez M, Devillier P, Advenier C, Candenas ML (2004) mRNA expression of tachykinins and tachykinin receptors in different human tissues. Eur J Pharmacol 494(2–3):233–239. doi:10.1016/j.ejphar.2004.05.016
Rameshwar P, Gascon P (1996) Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma. Blood 88(1):98–106
Rodriguez-Paredes M, Esteller M (2011) Cancer epigenetics reaches mainstream oncology. Nat Med 17(3):330–339. doi:10.1038/nm.2305
Rosso M, Munoz M, Berger M (2012) The role of neurokinin-1 receptor in the microenvironment of inflammation and cancer. Sci World J 2012:381434. doi:10.1100/2012/381434
Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V (2002) The tachykinin peptide family. Pharmacol Rev 54(2):285–322
Van Dyke DL, Worsham MJ, Benninger MS, Krause CJ, Baker SR, Wolf GT, Drumheller T, Tilley BC, Carey TE (1994) Recurrent cytogenetic abnormalities in squamous cell carcinomas of the head and neck region. Genes Chromosom Cancer 9(3):192–206
Vokes EE, Weichselbaum RR, Lippman SM, Hong WK (1993) Head and neck cancer. N Engl J Med 328(3):184–194. doi:10.1056/NEJM199301213280306
Xu C, Yaici ED, Conrath M, Blanchard P, Leclerc P, Benoit G, Verge D, Giuliano F (2005) Galanin and neurokinin-1 receptor immunoreactive [corrected] spinal neurons controlling the prostate and the bulbospongiosus muscle identified by transsynaptic labeling in the rat. Neuroscience 134(4):1325–1341. doi:10.1016/j.neuroscience.2005.06.002
Acknowledgments
The authors would like to thank Ms. Yuko Mohri for her excellent technical support. Authors received a Grant-in-Aid for Scientific Research (No. 23592524) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
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Misawa, K., Kanazawa, T., Misawa, Y. et al. Frequent promoter hypermethylation of tachykinin-1 and tachykinin receptor type 1 is a potential biomarker for head and neck cancer. J Cancer Res Clin Oncol 139, 879–889 (2013). https://doi.org/10.1007/s00432-013-1393-5
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DOI: https://doi.org/10.1007/s00432-013-1393-5