Larynx cancer: search for molecular markers
David Livingstone Alves Figueiredo, Bárbara Mendes Paz Chao, Felipe Nathan da Silva Figueiredo
Abstract
Introduction: Despite the advances in the understanding and treatment of the Larynx squamous cell carcinoma (LSCC), the survival has not changed in the last 30 years. Objective: In this study, we search for a better understanding of the pattern of genic expression of LSCC. Methods: Thirty-two tumor samples were collected from patients submitted to LSCC resection. The samples were submitted to cDNA microarray analysis to identify LSCC target. Results: The comparison of gene expression between early and advanced stages revealed 30 genes with significant differential expression. RT-qPCR validation experiments confirmed significant expression of only two genes (TMEM56 and SEC14L2) from eight selected. Comparing adjacent normal and tumor tissues, 69 genes showed statistically significant expression (mean ratio of 5.5), and 30 of them were up-regulated in tumor tissues. Gene expression validation by RT-qPCR showed SPRR2G and S100A7A as the most expressed in tumor tissue. Conclusion: The results demonstrate different pattern of expression, specially among tumor and non neoplastic tissue. The limitations to improve survival in larynx cancer justify studies focusing on search for molecular markers of prognosis and possible targeted therapy on LSCC
Keywords
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. http://dx.doi.org/10.3322/caac.21492. PMid:30207593.
2. Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ. Cancer statistics, 2004. CA Cancer J Clin. 2004;54(1):8-29. http://dx.doi.org/10.3322/canjclin.54.1.8. PMid:14974761.
3. Instituto Nacional de Câncer – INCA. Estimativas da incidência e mortalidade por câncer [Internet]. Rio de Janeiro: INCA; 2020 [cited 2019 June 30]. Available from: https://www.inca.gov.br/estimativa.
4. Hardisson D. Molecular pathogenesis of head and neck squamous cell carcinoma. Eur Arch Otorhinolaryngol. 2003;260(9):502-8. http://dx.doi.org/10.1007/s00405-003-0581-3. PMid:12736744.
5. Zhang SY, Lu ZM, Luo XN, Chen LS, Ge PJ, Song XH, Chen SH, Wu YL. Retrospective analysis of prognostic factors in 205 patients with laryngeal squamous cell carcinoma who underwent surgical treatment. PLoS One. 2013;8(4):e60157. http://dx.doi.org/10.1371/journal.pone.0060157. PMid:23593169.
6. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, Hamid O, Schuchter L, Cebon J, Ibrahim N, Kudchadkar R, Burris HA 3rd, Falchook G, Algazi A, Lewis K, Long GV, Puzanov I, Lebowitz P, Singh A, Little S, Sun P, Allred A, Ouellet D, Kim KB, Patel K, Weber J. Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations. N Engl J Med. 2012;367(18):1694-703. http://dx.doi.org/10.1056/NEJMoa1210093. PMid:23020132.
7. Petrelli F, Borgonovo K, Cabiddu M, Lonati V, Barni S. Relationship between skin rash and outcome in non-small-cell lung cancer patients treated with anti EGFR tyrosine kinase inhibitors: a literature-based meta-analysis of 24 trials. Lung Cancer. 2012;78(1):8-15. http://dx.doi.org/10.1016/j.lungcan.2012.06.009. PMid:22795701.
8. Cai J, Ma H, Huang F, Zhu D, Bi J, Ke Y, Zhang T. Correlation of bevacizumabinduced hypertension and outcomes of metastatic colorectal cancer patients treated with bevacizumab: a systematic review and meta-analysis. World J Surg Oncol. 2013;11(1):306. http://dx.doi.org/10.1186/1477-7819-11-306. PMid:24283603.
9. Gore L, DeGregori J, Porter CC. Targeting developmental pathways in children with cancer: what price success? Lancet Oncol. 2013;14(2):e70-8. http://dx.doi.org/10.1016/S1470-2045(12)70530-2. PMid:23369685.
10. Li X, Feng R, Huang C, Wang H, Wang J, Zhang Z, Yan H, Wen T. MicroRNA-351 regulates TMEM 59 (DCF1) expression and mediates neural stem cell morphogenesis. RNA Biol. 2012;9(3):292-301. http://dx.doi.org/10.4161/rna.19100. PMid:22336716.
11. Mesfin F. Decreased levels of expression of transmembrane protein 56 (TMEM56) in breast cancer tissues [thesis]. Los Angeles: University of Southern California; 2014. http://dx.doi.org/10.25549/usctheses-c3-458722.
12. Endoh Y, Tamura G, Watanabe H, Motoyama T. Author’s reply. J Pathol. 2000;191(4):467-8. http://dx.doi.org/10.1002/1096-9896(200008)191:4<467::AIDPATH627>3.0.CO;2-M. PMid:10918225.
13. Allen-Baume V, Ségui B, Cockcroft S. Current thoughts on the phosphatidylinositol transfer protein family. FEBS Lett. 2002;531(1):74-80. http://dx.doi.org/10.1016/S0014-5793(02)03412-9. PMid:12401207.
14. Habermehl D, Kempna P, Azzi A, Zingg JM. Recombinant SEC14-like proteins (TAP) possess GTPase activity. Biochem Biophys Res Commun. 2005;326(1):254-9. http://dx.doi.org/10.1016/j.bbrc.2004.11.021. PMid:15567179.
15. Cockcroft S. The diverse functions of phosphatidylinositol transfer proteins. Curr Top Microbiol Immunol. 2012;362:185-208. http://dx.doi.org/10.1007/978-94-007-5025-8_9. PMid:23086419.
16. Gong B, Li Z, Xiao W, Li G, Ding S, Meng A, Jia S. Sec14l3 potentiates VEGFR2 signaling to regulate zebrafish vasculogenesis. Nat Commun. 2019;10(1):1606. http://dx.doi.org/10.1038/s41467-019-09604-0. PMid:30962435.
17. Micci F, Panagopoulos I, Haugom L, Dahlback H-SS, Pretorius ME, Davidson B, Abeler VM, Tropé CG, Danielsen HE, Heim S. Genomic aberration patterns and expression profiles of squamous cell carcinomas of the vulva. Genes Chromosomes Cancer. 2013;52(6):551-63. http://dx.doi.org/10.1002/gcc.22053. PMid:23404381.
18. Liu Y, Cui J, Tang YL, Huang L, Zhou CY, Xu JX. Prognostic roles of mRNA expression of S100 in non-small-cell lung cancer. BioMed Res Int. 2018;2018:9815806. http://dx.doi.org/10.1155/2018/9815806.
19. Wang T, Liang Y, Thakur A, Zhang S, Liu F, Khan H, Shi P, Wang N, Chen M, Ren H. Expression and clinicopathological significance of S100 calcium binding protein A2 in lung cancer patients of Chinese Han ethnicity. Clin Chim Acta. 2017;464:118-22. http://dx.doi.org/10.1016/j.cca.2016.11.027. PMid:27876462.
20. Woo T, Okudela K, Mitsui H, Tajiri M, Rino Y, Ohashi K, Masuda M. Up-regulation of S100A11 in lung adenocarcinoma-its potential relationship with cancer progression. PLoS One. 2015;10(11):e0142642. http://dx.doi.org/10.1371/journal.pone.0142642. PMid:26544866.
21. Cross SS, Hamdy FC, Deloulme JC, Rehman I. Expression of S100 proteins in normal human tissues and common cancers using tissue microarrays: S100A6, S100A8, S100A9 and S100A11 are all overexpressed in common cancers. Histopathology. 2005;46(3):256-69. http://dx.doi.org/10.1111/j.1365-2559.2005.02097.x. PMid:15720411.
22. Tian T, Liu Z, Chen H, Cui Z. S100A1 promotes cell proliferation and migration and is associated with lymph node metastasis in ovarian cancer. Discov Med. 2017;23(127):235. PMid:28595036
23. Tian T, Li X, Hua Z, Ma J, Liu Z, Chen H, Cui Z. Reduction in migratory phenotype in a metastasized breast cancer cell line via downregulation of S100A4 and GRM3. Sci Rep. 2017;7(1):3459. http://dx.doi.org/10.1038/s41598-017-03811-9. PMid:28615627.
24. Zhang H, Wang Y, Chen Y, Sun S, Li N, Lv D, Liu C, Huang L, He D, Xiao X. Identification and validation of S100A7 associated with lung squamous cell carcinom metastasis to brain. Lung Cancer. 2007;57(1):37-45. http://dx.doi.org/10.1016/j. lungcan.2007.02.020. PMid:17418446.
25. Nasser MW, Wani NA, Ahirwar DK, Powell CA, Ravi J, Elbaz M, Zhao H, Padilla L, Zhang X, Shilo K, Ostrowski M, Shapiro C, Carson WE 3rd, Ganju RK. RAGE mediates S100A7-induced breast cancer growth and metastasis by modulating the tumor microenvironment. Cancer Res. 2015;75(6):974-85. http://dx.doi.org/10.1158/0008-5472.CAN-14-2161. PMid:25572331.
26. Liu G, Wu Q, Liu G, Song X, Zhang J. Knockdown of S100A7 reduces lung squamous cell carcinoma cell growth in vitro and in vivo. Int J Clin Exp Pathol. 2014;7(11):8279-89. PMid:25550886.
27. Tripathi SC, Matta A, Kaur J, Grigull J, Chauhan SS, Thakar A, Shukla NK, Duggal R, DattaGupta S, Ralhan R, Siu KWM. Nuclear S100A7 is associated with poor prognosis in head and neck cancer. PLoS One. 2010;5(8):e11939. http://dx.doi.org/10.1371/journal.pone.0011939. PMid:20689826.
28. Silveira NJF, Varuzza L, Machado-Lima A, Lauretto MS, Pinheiro DG, Rodrigues RV, Severino P, Nobrega FG, Silva WA Jr, Pereira CAB, Tajara EH. Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries. BMC Med Genomics. 2008;1(1):56-73. http://dx.doi.org/10.1186/1755-8794-1-56. PMid:19014460.
29. Tiveron RC, Freitas LC, Figueiredo DL, Serafini LN, Mamede RC, Zago MA. Expression of calcium binding protein S100 A7 (psoriasin) in laryngeal carcinoma. Rev Bras Otorrinolaringol. 2012;78(4):59-65. PMid:22936138.
30. Dahlmann M, Kobelt D, Walther W, Mudduluru G, Stein U. S100A4 in cancer metastasis: Wnt signaling-driven interventions for metastasis restriction. Cancers. 2016;8(6):E59. http://dx.doi.org/10.3390/cancers8060059. PMid:27331819.
31. Stewart RL, Carpenter BL, West DS, Knifley T, Liu L, Wang C, Weiss HL, Gal TS, Durbin EB, Arnold SM, O’Connor KL, Chen M. S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDAapproved anti-helminthic agent niclosamide. Oncotarget. 2016;7(23):34630-42. http:// dx.doi.org/10.18632/oncotarget.8969. PMid:27127879.
32. Burock S, Daum S, Keilholz U, Neumann K, Walther W, Stein U. Phase II trial to investigate the safety and efficacy of orally applied niclosamide in patients with metachronous or sychronous metastases of a colorectal cancer progressing after therapy: the NIKOLO tria. BMC Cancer. 2018;18(1):297. http://dx.doi.org/10.1186/s12885-018-4197-9. PMid:29544454.
33. Bueno RBL, Ramão A, Pinheiro DG, Alves CP, Kannen V, Jungbluth AA, Araújo LF, Muys BR, Fonseca AS, Plaça JR, Panepucci RA, Neder L, Saggioro FP, Mamede RC, Figueiredo DL, Silva WA Jr. HOX genes: potential candidates for the progression of laryngeal squamous cell carcinoma. Tumour Biol. 2016;37(11):15087-96. http://dx.doi.org/10.1007/s13277-016-5356-8. PMid:27658780.
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