IADR Abstract Archives
Epigenetic Silencing of TGM2 Correlates With Poor HPV-Positive HNC Prognosis
Objectives: Introduction: Human papilloma virus (HPV) in head and neck cancer (HNC) are increasing significantly in the last decades. The objective of this study was to evaluate the DNA methylation alteration in HNC patients following their characterization based on risk factors.
Methods: Methods: Bisulfite converted DNA from 24 patients were hybridized in the Human_Methylation_450_BeadChip microarrays. qRT-PCR was used to validate the expression of genes containing differentially methylated regions (DMRs). Protein validation was performed by immunohistochemistry on the two candidate proteins, using an independent cohort of 100 HNC patients. The resulting data were correlated with clinicopathological outcomes.
Results: Result: We identified 2,655 DMPs located at 1,073 genes, being 384 hypomethylated and 2,271 hypermethylated CpG sites. Considering only the risk factors (high-risk versus low-risk), it was identified 15 DMRs located at promoter regions of 12 genes. From the 12 genes (ZNF323, FBXO39, SLFN12, TGM2, ZAP70, STK32B, HOXA2, LMO3, C1orf74, ST8SIA4, C12orf42, and PITX2), we confirmed a concordant mRNA expression for 8 genes (ZNF323, FBXO39, TGM2, ZAP70, LMO3, C1orf74, C12orf42, and PITX2). PITX2 and TGM2 were selected for validation in a large cohort and showed overexpression in HPV-negative and HPV-positive HNC respectively. This overexpression was associated with advanced tumor stage (P=0.0042). Our data was also independently validated in The Cancer Genome Atlas (TCGA) platform using 530 HNC samples.
Conclusions: Conclusion: PITX2 and TGM2 were identified as the key candidates in HPV-negative and HPV-positive HNC respectively. The roles of these genes in tumor development and HNC progression should now be evaluated as well as the potential for prognostic predictor in HPV-positive HNC.
Methods: Methods: Bisulfite converted DNA from 24 patients were hybridized in the Human_Methylation_450_BeadChip microarrays. qRT-PCR was used to validate the expression of genes containing differentially methylated regions (DMRs). Protein validation was performed by immunohistochemistry on the two candidate proteins, using an independent cohort of 100 HNC patients. The resulting data were correlated with clinicopathological outcomes.
Results: Result: We identified 2,655 DMPs located at 1,073 genes, being 384 hypomethylated and 2,271 hypermethylated CpG sites. Considering only the risk factors (high-risk versus low-risk), it was identified 15 DMRs located at promoter regions of 12 genes. From the 12 genes (ZNF323, FBXO39, SLFN12, TGM2, ZAP70, STK32B, HOXA2, LMO3, C1orf74, ST8SIA4, C12orf42, and PITX2), we confirmed a concordant mRNA expression for 8 genes (ZNF323, FBXO39, TGM2, ZAP70, LMO3, C1orf74, C12orf42, and PITX2). PITX2 and TGM2 were selected for validation in a large cohort and showed overexpression in HPV-negative and HPV-positive HNC respectively. This overexpression was associated with advanced tumor stage (P=0.0042). Our data was also independently validated in The Cancer Genome Atlas (TCGA) platform using 530 HNC samples.
Conclusions: Conclusion: PITX2 and TGM2 were identified as the key candidates in HPV-negative and HPV-positive HNC respectively. The roles of these genes in tumor development and HNC progression should now be evaluated as well as the potential for prognostic predictor in HPV-positive HNC.