Correlation of P38 Mitogen-Activated Protein Kinase Expression to Clinical Stage in Nasopharyngeal Carcinoma

Authors

  • Farhat Farhat Universitas Sumatera Utara Fakultas Kedokteran, Otorhynolaryngology Head and Neck Surgery Jl. Dr. T. Mansyur No. 9, Medan, North Sumatera 20155, Indonesia
  • Elvita Rahmi Daulay Universitas Sumatera Utara Fakultas Kedokteran, Radiology Medan, North Sumatera, Indonesia
  • Jessy Chrestella Universitas Sumatera Utara Fakultas Kedokteran, Pathology Medan, Sumatera Utara, Indonesia
  • Rizalina Arwinati Asnir Universitas Sumatera Utara Fakultas Kedokteran, Otorhynolaryngology Head and Neck Surgery Jl. Dr. T. Mansyur No. 9, Medan, North Sumatera 20155, Indonesia
  • Ashri Yudhistira Universitas Sumatera Utara Fakultas Kedokteran, Otorhynolaryngology Head and Neck Surgery Jl. Dr. T. Mansyur No. 9, Medan, North Sumatera 20155, Indonesia
  • Riko Radityatama Susilo Universitas Sumatera Utara Fakultas Kedokteran, Otorhynolaryngology Head and Neck Surgery Jl. Dr. T. Mansyur No. 9, Medan, North Sumatera 20155, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2018.355

Keywords:

p38 MAPK, Nasopharyngeal carcinoma, Clinical stage, Correlation, Biomarker

Abstract

BACKGROUND: Nasopharyngeal carcinoma (NPC) is uncommon and usually diagnosed at the advanced stage. A subfamily of mitogen-activated protein kinase which is called p38 mitogen-activated protein kinase (MAPK) involved in response to stress, and plays an important role in cell regulation. There is a suggestion that p38 mitogen-activated protein kinase could be a potential biomarker to determine the clinical stage of nasopharyngeal carcinoma.

AIM: The aim of this study is for observing and analysing the correlation of p38 mitogen-activated protein kinase expression in regards to nasopharyngeal carcinoma patient’s clinical stage.

METHODS: This study involved 126 nasopharyngeal carcinoma patients admitted to Haji Adam Malik General Hospital.

RESULTS: The result of this study indicates that nasopharyngeal carcinoma mostly found in the age group 41-60 years, male, non-keratinizing squamous cell carcinoma, and stage IV group. In immunohistochemistry evaluation, most of p38 mitogen-activated protein kinase overexpressed in non-keratinizing squamous cell carcinoma, T3-T4, N2-N3 and clinical stage III-IV. Spearman’s test for categorical correlation yield p-value of < 0.001.

CONCLUSION: In conclusion, there is a significant correlation between p38 mitogen-activated protein kinase expression and the clinical stage of nasopharyngeal carcinoma.

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References

Adham M, Kurniawan AN, Muhtadi AI, Roezin A, Hermani B, Gondhowiardjo S, et al. Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence, signs, and symptoms at presentation. Chinese journal of cancer. 2012; 31(4):185. https://doi.org/10.5732/cjc.011.10328 PMid:22313595 PMCid:PMC3777476

Tang L-L, Chen W-Q, Xue W-Q, He Y-Q, Zheng R-S, Zeng Y-X, et al. Global trends in incidence and mortality of nasopharyngeal carcinoma. Cancer letters. 2016;374(1):22-30.Torre LA, Bray F, Siegel RL, Ferlay J, Lortetâ€Tieulent J, Jemal A. Global cancer statistics, 2012. CA: a cancer journal for clinicians. 2015; 65(2):87-108.

Cao S-M, Simons MJ, Qian C-N. The prevalence and prevention of nasopharyngeal carcinoma in China. Chinese journal of cancer. 2011; 30(2):114. https://doi.org/10.5732/cjc.010.10377 PMCid:PMC4013340

Zhang L-F, Li Y-H, Xie S-H, Ling W, Chen S-H, Liu Q, et al. Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County, Guangdong Province, South China: an age-period-cohort analysis. Chinese journal of cancer. 2015; 34(3):15. https://doi.org/10.1186/s40880-015-0018-6 PMid:26058679 PMCid:PMC4593377

Jayalie VF, Paramitha MS, Jessica J, Liu CA, Ramadianto AS, Trimartani T, et al. Profile of Nasopharyngeal Carcinoma in Dr. Cipto Mangunkusumo National Hospital, 2010. eJournal Kedokteran Indonesia. 2017:156-62.

Nawaz I, Moumad K, Martorelli D, Ennaji MM, Zhou X, Zhang Z, et al. Detection of nasopharyngeal carcinoma in Morocco (North Africa) using a multiplex methylation-specific PCR biomarker assay. Clinical epigenetics. 2015; 7(1):89. https://doi.org/10.1186/s13148-015-0119-8 PMid:26300994 PMCid:PMC4546349

Tulalamba W, Janvilisri T. Nasopharyngeal carcinoma signaling pathway: an update on molecular biomarkers. International journal of cell biology. 2012; 2012.

Fles R, Bos A, Rachmawati D, Waliyanti E, Tan I, Haryana S, et al. The role of Indonesian patients' health behaviors in delaying the diagnosis of nasopharyngeal carcinoma. BMC public health. 2017; 17(1):510. https://doi.org/10.1186/s12889-017-4429-y PMid:28545416 PMCid:PMC5445307

Tsang CM, Tsao SW. The role of Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma. Virologica Sinica. 2015; 30(2):107-21. https://doi.org/10.1007/s12250-015-3592-5 PMid:25910483

Zeng MS, Zeng YX. Pathogenesis and etiology of nasopharyngeal carcinoma. InNasopharyngeal Cancer 2010 (pp. 9-25). Springer, Berlin, Heidelberg.

Liu T-H, Zheng F, Cai M-Y, Guo L, Lin H-X, Chen J-W, et al. The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis. Oncotarget. 2016; 7(18):25836. https://doi.org/10.18632/oncotarget.8283 PMid:27028992 PMCid:PMC5041948

Petersson F, Editor. Nasopharyngeal carcinoma: a review. Seminars in diagnostic pathology. Elsevier, 2015.

Young LS, Dawson CW. Epstein-Barr virus and nasopharyngeal carcinoma. Chinese journal of cancer. 2014; 33(12):581. https://doi.org/10.5732/cjc.014.10197

Burgos JS. Involvement of the Epstein-Barr virus in the nasopharyngeal carcinoma pathogenesis. Medical Oncology. 2005; 22(2):113-21. https://doi.org/10.1385/MO:22:2:113 PMid:28184182

Chan AT, Teo PM, Huang DP. Pathogenesis and treatment of nasopharyngeal carcinoma. InSeminars in oncology 2004 Dec 1 (Vol. 31, No. 6, pp. 794-801). WB Saunders.

Raab-Traub N, editor. Epstein–Barr virus in the pathogenesis of NPC. Seminars in cancer biology. Elsevier, 2002.

Yong H-Y, Koh M-S, Moon A. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Expert opinion on investigational drugs. 2009; 18(12):1893-905. https://doi.org/10.1517/13543780903321490 PMid:19852565

Martínâ€Blanco E. p38 MAPK signalling cascades: ancient roles and new functions. Bioessays. 2000; 22(7):637-45. https://doi.org/10.1002/1521-1878(200007)22:7<637::AID-BIES6>3.0.CO;2-E

Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiology and molecular biology reviews. 2011; 75(1):50-83. https://doi.org/10.1128/MMBR.00031-10 PMid:21372320 PMCid:PMC3063353

Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue–a review. Diagnostic pathology. 2014; 9(1):221. https://doi.org/10.1186/s13000-014-0221-9 PMid:25432701 PMCid:PMC4260254

Cuadrado A, Nebreda AR. Mechanisms and functions of p38 MAPK signalling. Biochemical Journal. 2010; 429(3):403-17. https://doi.org/10.1042/BJ20100323 PMid:20626350

Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiology and molecular biology reviews. 2004; 68(2):320-44. https://doi.org/10.1128/MMBR.68.2.320-344.2004 PMid:15187187 PMCid:PMC419926

Wagner EF, Nebreda ÃR. Signal integration by JNK and p38 MAPK pathways in cancer development. Nature Reviews Cancer. 2009; 9(8):537. https://doi.org/10.1038/nrc2694 PMid:19629069

Obata T, Brown GE, Yaffe MB. MAP kinase pathways activated by stress: the p38 MAPK pathway. Critical care medicine. 2000; 28(4):N67-N77. https://doi.org/10.1097/00003246-200004001-00008 PMid:10807318

Coulthard LR, White DE, Jones DL, McDermott MF, Burchill SA. p38MAPK: stress responses from molecular mechanisms to therapeutics. Trends in molecular medicine. 2009; 15(8):369-79. https://doi.org/10.1016/j.molmed.2009.06.005 PMid:19665431 PMCid:PMC3016890

Bradham C, McClay DR. p38 MAPK in development and cancer. Cell cycle. 2006; 5(8):824-8. https://doi.org/10.4161/cc.5.8.2685 PMid:16627995

Wang B, Jiang H, Ma N, Wang Y. Phosphorylated-p38 mitogen-activated protein kinase expression is associated with clinical factors in invasive breast cancer. Springer Plus. 2016; 5(1):934. https://doi.org/10.1186/s40064-016-2636-0 PMid:27386378 PMCid:PMC4929108

Olson JM, Hallahan AR. p38 MAP kinase: a convergence point in cancer therapy. Trends in molecular medicine. 2004; 10(3):125-9. https://doi.org/10.1016/j.molmed.2004.01.007 PMid:15102355

Leelahavanichkul K, Amornphimoltham P, Molinolo AA, Basile JR, Koontongkaew S, Gutkind JS. A role for p38 MAPK in head and neck cancer cell growth and tumorâ€induced angiogenesis and lymphangiogenesis. Molecular oncology. 2014; 8(1):105-18. https://doi.org/10.1016/j.molonc.2013.10.003 PMid:24216180 PMCid:PMC3946852

Kennedy NJ, Cellurale C, Davis RJ. A radical role for p38 MAPK in tumor initiation. Cancer Cell. 2007; 11(2):101-3. https://doi.org/10.1016/j.ccr.2007.01.009 PMid:17292820

Riebe C, Pries R, Schroeder KN, Wollenberg B. Phosphorylation of STAT3 in head and neck cancer requires p38 MAPKinase, whereas phosphorylation of STAT1 occurs via a different signaling pathway. Anticancer research. 2011; 31(11):3819-25. PMid:22110204

Beisswenger C, Coyne CB, Shchepetov M, Weiser JN. Role of p38 MAP kinase and transforming growth factor-β signaling in transepithelial migration of invasive bacterial pathogens. Journal of Biological Chemistry. 2007; 282(39):28700-8. https://doi.org/10.1074/jbc.M703576200 PMid:17650505

Lara HHR, Monroy A. Prevalence of nasopharyngeal carcinoma among patients with nasopharyngeal mass in a Philippine tertiary training hospital. Philippine Journal of Otolaryngology Head and Neck Surgery. 2016; 31(1):35-8.

Han J, Sun P. The pathways to tumor suppression via route p38. Trends in biochemical sciences. 2007; 32(8):364-71. https://doi.org/10.1016/j.tibs.2007.06.007 PMid:17624785

Lin ML, Lu YC, Chung JG, Wang SG, Lin HT, Kang SE, et al. Downâ€regulation of MMPâ€2 through the p38 MAPKâ€NFâ€ÎºBâ€dependent pathway by aloeâ€emodin leads to inhibition of nasopharyngeal carcinoma cell invasion. Molecular carcinogenesis. 2010; 49(9):783-97. https://doi.org/10.1002/mc.20652

Zhong Y, Naito Y, Cope L, Naranjo-Suarez S, Saunders T, Hong S-M, et al. Functional p38 MAPK identified by biomarker profiling of pancreatic cancer restrains growth through JNK inhibition and correlates with improved survival. Clinical cancer research. 2014; 20(23):6200-11. https://doi.org/10.1158/1078-0432.CCR-13-2823 PMid:24963048 PMCid:PMC4866510

Zhu G-H, Dai H-P, Shen Q, Ji O, Zhang Q, Zhai Y-L. Curcumin induces apoptosis and suppresses invasion through MAPK and MMP signaling in human monocytic leukemia SHI-1 cells. Pharmaceutical biology. 2016; 54(8):1303-11. PMid:26134921

Bistrović A, GrbÄić P, Harej A, Sedić M, Kraljević-Pavelić S, KoÅ¡trun S, et al. Small molecule purine and pseudopurine derivatives: synthesis, cytostatic evaluations and investigation of growth inhibitory effect in non-small cell lung cancer A549. Journal of enzyme inhibition and medicinal chemistry. 2018; 33(1):271-85. https://doi.org/10.1080/14756366.2017.1414807 PMid:29271659 PMCid:PMC6009932

Wakeman D, Schneider JE, Liu J, Wandu WS, Erwin CR, Guo J, et al. Deletion of p38- alpha mitogen-activated protein kinase within the intestinal epithelium promotes colon tumorigenesis. Surgery. 2012; 152(2):286-93. https://doi.org/10.1016/j.surg.2012.05.009 PMid:22828150 PMCid:PMC3408636

Published

2018-11-19

How to Cite

1.
Farhat F, Daulay ER, Chrestella J, Asnir RA, Yudhistira A, Susilo RR. Correlation of P38 Mitogen-Activated Protein Kinase Expression to Clinical Stage in Nasopharyngeal Carcinoma. Open Access Maced J Med Sci [Internet]. 2018 Nov. 19 [cited 2022 May 21];6(11):1982-5. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2018.355

Issue

Section

A - Basic Science

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