Genomic and epigenetic signatures associated with survival rate in oral squamous cell carcinoma patients

Abstract

Purpose: Although oral squamous cell carcinoma (OSCC) presents great mortality and morbidity worldwide, the mechanisms behind its clinical behavior remain unclear. Biomarkers are needed to forecast patients' survival and, among those patients undergoing curative therapy, which are more likely to develop tumor recurrence/metastasis. Demonstrating clinical relevance of these biomarkers could be crucial both for surveillance and in helping to establish adjuvant therapy strategies. We aimed to identify genomic and epigenetic biomarkers of OSCC prognosis as well as to explore a noninvasive strategy to perform its detection.Methods: OSCC tumor and non-tumor tissue samples and cells scrapped from the tumor surface were genomic and epigenetically evaluated by Methylation-Specific Multiplex Ligation-dependent Probe Amplification technique.Results: Copy number alterations in ATM, CASR, TP73, CADM1, RARB, CDH13, PAX5, RB1 genes and GATA5, PAX6, CADM1 and CHFR promoter methylation were shown to be associated with worse OSCC patients' survival. Copy number alterations in BRCA1, CDKN2A, CHFR, GATA5, PYCARD, STK11, TP53, VHL genes and GATA5, CADM1, KLLN, MSH6, PAX5, WT1 promoter methylation were shown to be associated with development of metastasis/relapses during or after OSCC patients' treatment. We also found a good agreement in the status of CDKN2A promoter methylation evaluated noninvasively or in the tumor tissue.Conclusions: Genomic and epigenetic signatures were validated in a larger and geographically separate cohort, from TCGA database, which reinforce their clinical applicability. Noninvasive methodologies for detection of these signatures require further studies before translation in to clinical practice.

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

“…The survival difference between the two identified clusters, cluster 4 vs. cluster 6, represented a clear difference in the lifetime of these patients. These results fall in agreement with previous reports that showed a significant association between promoter methylation status and worse OSCC patients' survival [31][32][33][34]. These results demonstrated the utility of epigenetic alterations detection for potential clinical application in OSCC patients.…”

“…Many laboratories have discovered oncogenes and tumor suppressors for OSCC. However, cumulative evidence revealed more complex mechanisms underlying the development and progression of this disease, including, among others, interactions between genomic and epigenetic alterations [28][29][30][31] Epigenetic alterations are responsible for the regulation of ontologically-related gene expression networks, at an appropriate level of environmental conditions and time, leading to a rise of both normal and diseased phenotype development.…”

JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients

“…Dysregulated expression of PAX5 is involved in differentiation block (55), somatic hypermutation and immunoglobulin heavy chain class switch recombination (56), leukemogenesis (57), and positive regulation of c-Met transcription (58). PAX5 association to different tumor types suggests it has diagnostic or prognostic utility in lung cancer (59), Hodgkin lymphoma (60), acute lymphocytic leukemia (61), breast cancer (61), oral cancer (62,63), gastric cancer (64), head and neck cancer (65,66), and esophageal cancer (66). A recent study demonstrated that the lack of expression of PAX5 in lymphoid neoplasms is associated with promoter hypermethylation, leading to PAX5 silencing in cases characterized by poor clinical outcome (67).…”

Meso-tetra(4-carboxyphenyl)porphine-Enhanced DNA Methylation Sensing Interface on a Light-Addressable Potentiometric Sensor

“…It has been accepted that understanding the DNAm degree in a certain genomic DNA sequence is conducive to the early diagnosis and treatment of disease. 5 Therefore, an effective technology to profile the landscape of genomic methylation is necessary. Lots of conventional approaches have been extensively developed for the determination of DNAm, such as methylation-specific polymerase chain reaction (PCR), 6 bisulfite conversion (BC), 7 fluorescence assay, 8 high-performance liquid chromatography, 9 and mass spectroscopy.…”