Prognostic Potential of KLOTHO and SFRP1 Promoter Methylation in Head and Neck Squamous Cell Carcinoma

Overview

Journal J Appl Genet

Publisher Springer

Specialty Genetics

Date 2017 Aug 17

PMID 28812223

Citations 6

Authors

Abeer A Alsofyani

Rawiah A Alsiary

Alaa Samkari

Baraa T Alhaj-Hussain

Jalaluddin Azam Khan

Jaudah Al-Maghrabi

Aisha Elaimi

Mohammed H Al-Qahtani

Adel M Abuzenadah

Ashraf Dallol

Affiliations

Soon will be listed here.

Abstract

Hypermethylation in the CpG island promoter regions of tumor suppressors is known to play a significant role in the development of HNSCC and the detection of which can aid the classification and prognosis of HNSCC. This study aims to profile the methylation patterns in a panel of key genes including CDKN2A, CDKN2B, KLOTHO (KL), RASSF1A, RARB, SLIT2, and SFRP1, in a group of HNSCC samples from Saudi Arabia. The extent of methylation in these genes is determined using the MethyLight assay and correlated with known clinicopathological parameters in our samples of 156 formalin-fixed and paraffin-embedded HNSCC tissues. SLIT2 methylation had the highest frequency (64.6%), followed by RASSF1A (41.3%), RARB (40.7%), SFRP1 (34.9), KL (30.7%), CKDN2B (29.6%), and CKDN2A (29.1%). KL and SFRP1 methylation were more predominant in nasopharyngeal tumors (P = 0.001 and P = 0.031 respectively). Kaplan Meier analysis showed that patients with moderately differentiated tumors who display SFRP1 methylation have significantly worse overall survival in comparison with other samples. In contrast, better clinical outcomes were seen in patients with KL methylation. In conclusion, our findings suggest that the detection of frequent methylation in SFRP1 and KL genes' promoters could serve as prognostic biomarkers for HNSCC.

Citing Articles

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Role of Fibroblast Growth Factor 23 (FGF23) and αKlotho in Cancer.

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Epigenetic Modifications in Head and Neck Cancer.

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Prognostic Relevance of SFRP1 Gene Promoter Methylation in Colorectal Carcinoma.

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DNA methylation-mediated Klotho silencing is an independent prognostic biomarker of head and neck squamous carcinoma.

Zhu Y, Cao X, Zhang X, Chen Q, Wen L, Wang P Cancer Manag Res. 2019; 11:1383-1390.

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References

Xie B, Zhou J, Yuan L, Ren F, Liu D, Li Q . Epigenetic silencing of Klotho expression correlates with poor prognosis of human hepatocellular carcinoma. Hum Pathol. 2012; 44(5):795-801. DOI: 10.1016/j.humpath.2012.07.023. View

Demokan S, Dalay N . Role of DNA methylation in head and neck cancer. Clin Epigenetics. 2012; 2(2):123-50. PMC: 3365391. DOI: 10.1007/s13148-011-0045-3. View

Majchrzak-Celinska A, Slocinska M, Barciszewska A, Nowak S, Baer-Dubowska W . Wnt pathway antagonists, SFRP1, SFRP2, SOX17, and PPP2R2B, are methylated in gliomas and SFRP1 methylation predicts shorter survival. J Appl Genet. 2015; 57(2):189-97. PMC: 4830852. DOI: 10.1007/s13353-015-0312-7. View

Marsit C, Karagas M, Andrew A, Liu M, Danaee H, Schned A . Epigenetic inactivation of SFRP genes and TP53 alteration act jointly as markers of invasive bladder cancer. Cancer Res. 2005; 65(16):7081-5. DOI: 10.1158/0008-5472.CAN-05-0267. View

Economopoulou P, Perisanidis C, Giotakis E, Psyrri A . The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications. Ann Transl Med. 2016; 4(9):173. PMC: 4876265. DOI: 10.21037/atm.2016.03.34. View

Czerninski R, Krichevsky S, Ashhab Y, Gazit D, Patel V, Ben-Yehuda D . Promoter hypermethylation of mismatch repair genes, hMLH1 and hMSH2 in oral squamous cell carcinoma. Oral Dis. 2009; 15(3):206-13. DOI: 10.1111/j.1601-0825.2008.01510.x. View

Stadler M, Patel M, Couch M, Hayes D . Molecular biology of head and neck cancer: risks and pathways. Hematol Oncol Clin North Am. 2008; 22(6):1099-124, vii. PMC: 2630967. DOI: 10.1016/j.hoc.2008.08.007. View

Fendri A, Masmoudi A, Khabir A, Sellami-Boudawara T, Daoud J, Frikha M . Inactivation of RASSF1A, RARbeta2 and DAP-kinase by promoter methylation correlates with lymph node metastasis in nasopharyngeal carcinoma. Cancer Biol Ther. 2009; 8(5):444-51. DOI: 10.4161/cbt.8.5.7686. View

Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, Mori M . 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. 2003; 63(13):3724-8. View

10.

Meng R, Li Y, Chen X, Huang Y, Shi H, Du D . Aberrant Methylation of RASSF1A Closely Associated with HNSCC, a Meta-Analysis. Sci Rep. 2016; 6:20756. PMC: 4746596. DOI: 10.1038/srep20756. View

11.

Rubinek T, Shulman M, Israeli S, Bose S, Avraham A, Zundelevich A . Epigenetic silencing of the tumor suppressor klotho in human breast cancer. Breast Cancer Res Treat. 2011; 133(2):649-57. DOI: 10.1007/s10549-011-1824-4. View

12.

Jones P, Baylin S . The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002; 3(6):415-28. DOI: 10.1038/nrg816. View

13.

Kinoshita T, Hanazawa T, Nohata N, Kikkawa N, Enokida H, Yoshino H . Tumor suppressive microRNA-218 inhibits cancer cell migration and invasion through targeting laminin-332 in head and neck squamous cell carcinoma. Oncotarget. 2012; 3(11):1386-400. PMC: 3717800. DOI: 10.18632/oncotarget.709. View

14.

Cai F, Xiao X, Niu X, Shi H, Zhong Y . Aberrant Methylation of MGMT Promoter in HNSCC: A Meta-Analysis. PLoS One. 2016; 11(9):e0163534. PMC: 5033341. DOI: 10.1371/journal.pone.0163534. View

15.

Ren X, Zhou G, Jiang W, Sun Y, Xu Y, Li Y . Low SFRP1 Expression Correlates with Poor Prognosis and Promotes Cell Invasion by Activating the Wnt/β-Catenin Signaling Pathway in NPC. Cancer Prev Res (Phila). 2015; 8(10):968-77. DOI: 10.1158/1940-6207.CAPR-14-0369. View

16.

Lee J, Jeong D, Kim J, Lee S, Park J, Chang B . The anti-aging gene KLOTHO is a novel target for epigenetic silencing in human cervical carcinoma. Mol Cancer. 2010; 9:109. PMC: 2885346. DOI: 10.1186/1476-4598-9-109. View

17.

Lee A, Poon Y, Foo W, Law S, Cheung F, Chan D . Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure. Int J Radiat Oncol Biol Phys. 1992; 23(2):261-70. DOI: 10.1016/0360-3016(92)90740-9. View

18.

Marsit C, McClean M, Furniss C, Kelsey K . Epigenetic inactivation of the SFRP genes is associated with drinking, smoking and HPV in head and neck squamous cell carcinoma. Int J Cancer. 2006; 119(8):1761-6. DOI: 10.1002/ijc.22051. View

19.

Rigi-Ladiz M, Kordi-Tamandani D, Torkamanzehi A . Analysis of hypermethylation and expression profiles of APC and ATM genes in patients with oral squamous cell carcinoma. Clin Epigenetics. 2012; 3:6. PMC: 3303468. DOI: 10.1186/1868-7083-3-6. View

20.

Dallol A, Buhmeida A, Merdad A, Al-Maghrabi J, Gari M, Abu-Elmagd M . Frequent methylation of the KLOTHO gene and overexpression of the FGFR4 receptor in invasive ductal carcinoma of the breast. Tumour Biol. 2015; 36(12):9677-83. DOI: 10.1007/s13277-015-3733-3. View