Abstract
Background: Prognosis of oral squamous cell carcinoma (OSCC) is difficult to exactly assess on pre-operative biopsies. Since OSCC DNA methylation profile has proved to be a useful pre-operative diagnostic tool, the aim of the present study was to evaluate the prognostic impact of DNA methylation profile to discriminate OSCC with high and low aggressive potential. Methods: 36 OSCC cases underwent neoplastic cells collection by gentle brushing of the lesion, before performing a pre-operative biopsy. The CpG islands methylation status of 13 gene (ZAP70, ITGA4, KIF1A, PARP15, EPHX3, NTM, LRRTM1, FLI1, MiR193, LINC00599, MiR296, TERT, GP1BB) was studied by bisulfite Next Generation Sequencing (NGS). A Cox proportional hazards model via likelihood-based component-wise boosting was used to evaluate the prognostic power of the CpG sites. Results: The boosting estimation identified five CpGs with prognostic significance: EPHX3-24, EPHX3-26, ITGA4-3, ITGA4-4, and MiR193-3. The combination of significant CpGs provided promising results for adverse events prediction (Brier score = 0.080, C-index = 0.802 and AUC = 0.850). ITGA4 had a strong prognostic power in patients with early OSCC. Conclusions: These data confirm that the study of methylation profile provides new insights into the molecular mechanisms of OSCC and can allow a better OSCC prognostic stratification even before surgery.
Highlights
Oral squamous cell carcinoma (OSCC) is the tenth most common cancer in the world
The boosting estimation resulted in five non-zero regression coefficients associated with EPHX3-24, EPHX3-26, ITGA4-3, ITGA4-4, and MiR193-3 significantly associated with the occurrence of loco regional adverse events
Prior studies have noted that the methylation of epoxide hydrolase 3 (EPHX3) is significantly associated with the prognosis of prostate cancer and its inclusion into clinical practice has been suggested as a tool to a more accurate prediction of which patients may experience prostate cancer recurrence
Summary
Oral squamous cell carcinoma (OSCC) is the tenth most common cancer in the world. The annual estimated incidence is approximately 389,000 per year [1]. Prevention, early detection, and adequate pre-operative diagnosis are needed to find out patients with high-risk lesions. Pre-operative biopsy of a suspected lesion in the oral cavity is necessary to confirm the diagnosis of OSCC but can give only limited information about pathological prognostic factors. There is a great need for strategies that can allow an accurate prognostic evaluation of OSCC aggressiveness pre-operatively. Prognosis of oral squamous cell carcinoma (OSCC) is difficult to exactly assess on pre-operative biopsies. Since OSCC DNA methylation profile has proved to be a useful pre-operative diagnostic tool, the aim of the present study was to evaluate the prognostic impact of DNA methylation profile to discriminate OSCC with high and low aggressive potential. Results: The boosting estimation identified five CpGs with prognostic significance: EPHX3-24, EPHX3-26, ITGA4-3, ITGA4-4, and MiR193-3. Conclusions: These data confirm that the study of methylation profile provides new insights into the molecular mechanisms of OSCC and can allow a better OSCC prognostic stratification even before surgery
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