Prognostic potential of KLOTHO and SFRP1 promoter methylation in head and neck squamous cell carcinoma
Journal of Applied Genetics
Alsofyani AA1, Alsiary RA1, Samkari A1, Alhaj-Hussain BT2, Khan JA3, Al-Maghrabi J4, Elaimi A5, Al-Qahtani MH5, Abuzenadah AM5, Dallol A6.
1 King Abdullah International Medical Research Center (KAIMRC) and King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, Kingdom of Saudi Arabia.
2 Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, National Guard Health Affairs, Mail Box No. 6277, Jeddah, Kingdom of Saudi Arabia.
3 Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
4 Department of Pathology, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
5 Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia.
6 Center of Excellence in Genomic Medicine Research, King Abdulaziz University, P.O. Box 80216, Jeddah, 21589, Kingdom of Saudi Arabia. email@example.com.
Year of Publication:
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.