Abstract
Cancer cells, including head and neck cancer cell carcinoma (HNSCC), are characterized by an increased telomerase activity. This enzymatic complex is active in approximately 80–90% of all malignancies, and is regulated by various factors, including methylation status of hTERT gene promoter. hTERT methylation pattern has been thoroughly studied so far. It was proved that hTERT is aberrantly methylated in tumor tissue versus healthy counterparts. However, such effect has not yet been investigated in PBLs (peripheral blood leukocytes) of cancer patients. The aim of this study was to analyze the hTERT gene promoter methylation status in blood leukocytes. DNA was extracted from PBL of 92 patients with histologically diagnosed HNSCC and 53 healthy controls. Methylation status of whole hTERT promoter fragment with independent analysis of each 19 CpG sites was performed using bisulfide conversion technique followed by sequencing of PCR products. Not significant (p = 0.0532) differences in the general frequency of hTERT CpG sites methylation were detected between patients and healthy controls. However, it was discovered that some of analyzed positions (CpG islands: 1 [p = 0.0235], 5 [p = 0.0462], 8 [p = 0.0343]) are significantly more often methylated in HNSCC patients than in controls. The opposite finding was observed in case of CpG position 2 (p = 0.0210). Furthermore, closer analysis of single CpG positions revealed differences in methylation status dependent on anatomical site and TNM classification. To conclude, hTERT promoter methylation status (general or single CpG sites) would be considered as a molecular markers of HNSCC diagnostics.
Highlights
Despite significant advances in science, cancer still remains a leading cause of mortality worldwide, yielding as many as 8.8 million deaths in 2015 (World Health Organization 2017)
Given the incoherence in literature data concerning human telomerase reverse transcriptase (hTERT) promoter methylation profile and its correlation with head and neck squamous cell carcinoma (HNSCC) incidence, we aimed to investigate whether hTERT promoter hypermethylation observed in cancer cells is reflected in peripheral blood leukocytes of HNSCC patients and could serve as a useful biomarker in screening or early diagnostics
We have investigated whether hTERT promoter methylation status assessment in PBL may significantly contribute to a diagnostic workup and/or allow to determine the prognosis in head and neck cancer patients
Summary
Despite significant advances in science, cancer still remains a leading cause of mortality worldwide, yielding as many as 8.8 million deaths in 2015 (World Health Organization 2017). In these terms, head and neck squamous cell carcinoma (HNSCC) is no exception, as it affects over 500,000 patients every year Diagnosis and prevention are crucial to HNSCC burden decrease and improvement of treatment outcomes (Leemans et al 2011), yet despite relatively easy access to oral cavity during examination, majority of cases are diagnosed at more advanced stages of the disease (Richards 2007). A search for accessible biomarkers, supplementing the information and facilitating personalized treatment is still ongoing
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