MAP2K6 is Associated with Radiation Resistance and Adverse Prognosis for Locally Advanced Nasopharyngeal Carcinoma Patients

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2018 Dec 28

PMID 30588096

Citations 13

Authors

Zhanzhan Li

Na Li

Liangfang Shen

Affiliations

Soon will be listed here.

Abstract

Background: Although radiotherapy is the primary therapeutic option for nasopharyngeal carcinoma (NPC), local recurrence and distant metastasis caused by radioresistance are still the major barriers for some NPC patients who cannot benefit from radiotherapy. In this study, we analyzed the association between MAP2K6 expression and radioresistance in patients with locally advanced NPC.

Methods: We collected 120 NPC patients who received radiotherapy in the Xiangya Hospital of Central South University from August 2008 to July 2012. The clinical data and tissue samples of patients were collected. Detection of MAP2K6 was performed using immunohistochemical staining.

Results: The rates of two groups were 19.4% and 4.2%, and significant difference was observed between MAP2K6 high expression group and low expression group (χ=5.817, =0.016). The Kaplan-Meier analysis suggested a significant difference in the survival rate between two groups (<0.05). The results from multivariate Cox regression indicated that the MAP2K6 was independently related to adverse prognosis in NCP patients (HR =3.40, 95% CI =1.13-10.26, =0.030).

Conclusion: The present study indicated that MAP2K6 was correlated with radioresistance, and the elevated expression of MAP2K6 predicted poor prognosis in NPC patients. MAP2K6 may be a new therapy target for radioresistance of NPC.

Citing Articles

WTAP-Mediated N6-Methyladenosine Modification Promotes Gastric Cancer Progression by Regulating MAP2K6 Expression.

Han S, Jiang H, Wang J, Li C, Liu T, Xuan M J Cancer. 2025; 16(5):1420-1437.

PMID: 39991580 PMC: 11843227. DOI: 10.7150/jca.98559.

The endogenous association among MMP2/miR-1248/Circ_0087558/miR-643/ MAP2K6 axis can contribute to brain metastasis in basal-like subtype of breast cancer.

Khoshbakht S, Zomorodi Anbaji F, Darzi M, Esmaeili R Heliyon. 2024; 10(13):e33195.

PMID: 39027611 PMC: 11255566. DOI: 10.1016/j.heliyon.2024.e33195.

Precision medicine in nasopharyngeal carcinoma: comprehensive review of past, present, and future prospect.

Siak P, Heng W, Teoh S, Lwin Y, Cheah S J Transl Med. 2023; 21(1):786.

PMID: 37932756 PMC: 10629096. DOI: 10.1186/s12967-023-04673-8.

Targeted therapy for head and neck cancer: signaling pathways and clinical studies.

Li Q, Tie Y, Alu A, Ma X, Shi H Signal Transduct Target Ther. 2023; 8(1):31.

PMID: 36646686 PMC: 9842704. DOI: 10.1038/s41392-022-01297-0.

Identification of Ten-Gene Related to Lipid Metabolism for Predicting Overall Survival of Breast Invasive Carcinoma.

Wang Z, Wang F Contrast Media Mol Imaging. 2022; 2022:8348780.

PMID: 35919504 PMC: 9293542. DOI: 10.1155/2022/8348780.

References

DeNittis A, Liu L, Rosenthal D, Machtay M . Nasopharyngeal carcinoma treated with external radiotherapy, brachytherapy, and concurrent/adjuvant chemotherapy. Am J Clin Oncol. 2002; 25(1):93-5. DOI: 10.1097/00000421-200202000-00020. View

Yu M, Yuan J . Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002; 12(6):421-9. DOI: 10.1016/s1044579x02000858. View

Song T, Liang B, Huang S, Xie B, Ding Z, Shen J . [Magnetic resonance imaging manifestations of radiation injury in brain stem and cervical spinal cord of nasopharyngeal carcinoma patients after radiotherapy]. Ai Zheng. 2005; 24(3):357-61. View

Yoshizawa T, Hammaker D, Boyle D, Corr M, Flavell R, Davis R . Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytokine expression. J Immunol. 2009; 183(2):1360-7. PMC: 2744479. DOI: 10.4049/jimmunol.0900483. View

Remy G, Risco A, Inesta-Vaquera F, Gonzalez-Teran B, Sabio G, Davis R . Differential activation of p38MAPK isoforms by MKK6 and MKK3. Cell Signal. 2009; 22(4):660-7. DOI: 10.1016/j.cellsig.2009.11.020. View

Sturchler E, Feurstein D, McDonald P, Duckett D . Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation. Biochemistry. 2010; 49(19):4094-102. DOI: 10.1021/bi100010j. View

Guo-Qing P, Yuan Y, Cai-Gao Z, Hongling Y, Gonghua H, Yan T . A study of association between expression of hOGG1, VDAC1, HK-2 and cervical carcinoma. J Exp Clin Cancer Res. 2010; 29:129. PMC: 2949824. DOI: 10.1186/1756-9966-29-129. View

Galan-Moya E, de la Cruz-Morcillo M, Valero M, Callejas-Valera J, Melgar-Rojas P, Hernadez Losa J . Balance between MKK6 and MKK3 mediates p38 MAPK associated resistance to cisplatin in NSCLC. PLoS One. 2011; 6(12):e28406. PMC: 3229586. DOI: 10.1371/journal.pone.0028406. View

Yang S, Chen J, Guo Y, Lin H, Zhang Z, Feng G . Identification of prognostic biomarkers for response to radiotherapy by DNA microarray in nasopharyngeal carcinoma patients. Int J Oncol. 2012; 40(5):1590-600. DOI: 10.3892/ijo.2012.1341. View

10.

Kyriakis J, Avruch J . Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012; 92(2):689-737. DOI: 10.1152/physrev.00028.2011. View

11.

Humphreys J, Piala A, Akella R, He H, Goldsmith E . Precisely ordered phosphorylation reactions in the p38 mitogen-activated protein (MAP) kinase cascade. J Biol Chem. 2013; 288(32):23322-30. PMC: 3743502. DOI: 10.1074/jbc.M113.462101. View

12.

Sun X, Su S, Chen C, Han F, Zhao C, Xiao W . Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: an analysis of survival and treatment toxicities. Radiother Oncol. 2013; 110(3):398-403. DOI: 10.1016/j.radonc.2013.10.020. View

13.

Liu S, Tsang N, Chiang W, Chang K, Hsueh C, Liang Y . Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance. J Clin Invest. 2013; 123(12):5269-83. PMC: 3859424. DOI: 10.1172/JCI63428. View

14.

Parray A, Anjum Baba R, Bhat H, Wani L, Mokhdomi T, Mushtaq U . MKK6 is upregulated in human esophageal, stomach, and colon cancers. Cancer Invest. 2014; 32(8):416-22. DOI: 10.3109/07357907.2014.933236. View

15.

Zhong J, Kang J, Wang X, Jiang W, Liao H, Yuan J . TAT-OSBP-1-MKK6(E), a novel TAT-fusion protein with high selectivity for human ovarian cancer, exhibits anti-tumor activity. Med Oncol. 2015; 32(4):118. DOI: 10.1007/s12032-015-0495-0. View

16.

He Y, Zhou Q, Shen L, Zhao Y, Lei M, Wei R . A retrospective study of the prognostic value of MRI-derived residual tumors at the end of intensity-modulated radiotherapy in 358 patients with locally-advanced nasopharyngeal carcinoma. Radiat Oncol. 2015; 10:89. PMC: 4464998. DOI: 10.1186/s13014-015-0401-0. View

17.

Huang X, Liu M, Sun H, Wang F, Xie X, Chen X . HK2 is a radiation resistant and independent negative prognostic factor for patients with locally advanced cervical squamous cell carcinoma. Int J Clin Exp Pathol. 2015; 8(4):4054-63. PMC: 4466980. View

18.

Chua M, Wee J, Hui E, Chan A . Nasopharyngeal carcinoma. Lancet. 2015; 387(10022):1012-1024. DOI: 10.1016/S0140-6736(15)00055-0. View

19.

Liao H, Kang J, Jiang W, Deng C, Yuan J, Shuai R . Delivery of Constitutively Active Mutant MKK6(E) With TAT-OSBP Induces Apoptosis in Human Ovarian Carcinoma HO8910 Cells. Int J Gynecol Cancer. 2015; 25(9):1548-56. DOI: 10.1097/IGC.0000000000000538. View

20.

He Y, Wang Y, Shen L, Zhao Y, Cao P, Lei M . Prognostic value of the distance between the primary tumor and brainstem in the patients with locally advanced nasopharyngeal carcinoma. BMC Cancer. 2016; 16:114. PMC: 4756467. DOI: 10.1186/s12885-016-2148-x. View