PITX2andPANCRDNA methylation predicts overall survival in patients with head and neck squamous cell carcinoma

Abstract

BackgroundSquamous cell carcinoma of the head and neck region (HNSCC) is a common malignant disease accompanied by a high risk of local or distant recurrence after curative-intent treatment. Biomarkers that allow for the prediction of disease outcome can guide clinicians with respect to treatment and surveillance strategies. Here, the methylation status of PITX2 and an adjacent lncRNA (PANCR) were evaluated for their ability to predict overall survival in HNSCC patients.ResultsPITX2 hypermethylation was associated with a better overall survival (hazard ratio, HR = 0.51, 95%CI: 0.35-0.74, p<0.001), while PANCR hypermethylation was significantly associated with an increased risk of death (HR = 1.64, 95%CI: 1.12-2.39, p=0.010).MethodsQuantitative, methylation-specific real-time PCR assays for PITX2 and PANCR were employed to measure bisulfite-converted DNA from formalin-fixed, paraffin-embedded (FFPE) tissues in a cohort of 399 patients with localized or locally advanced HNSCC who received curative-intent treatment (surgery with optional adjuvant radiochemotherapy or definite radiochemotherapy).ConclusionsPITX2 and PANCR methylation status were shown to be independent predictors for overall survival in HNSCC patients. Tissue-based methylation testing could therefore potentially be employed to identify patients with a high risk for death who might benefit from a more radical or alternative treatment.

Identification of Deregulated Pathways, Key Regulators, and Novel miRNA-mRNA Interactions in HPV-Mediated Transformation

“…The tumor suppressive role of PITX2 in cervical cancer development is further supported by our previously published whole methylome data showing that the PITX2 promoter is highly methylated in high passages of our four cell lines but not in primary donor keratinocytes [16]. PITX2 hypermethylation has been described as a promising prognostic biomarker in cervical cancer as well as breast cancer, head and neck squamous cell carcinoma, and prostate cancer [38][39][40][41].…”

CpG location and methylation level are crucial factors for the early detection of oral squamous cell carcinoma in brushing samples using bisulfite sequencing of a 13-gene panel

“…Moreover, only one third of patients present with early stage disease (T1–2, N0), and for the remainder, life expectancy is very short. Different researchers, including our group, have recently proposed an attractive strategy to reduce the burden of OSCC by analyzing the methylation status of a panel of genes starting from saliva and/or brushing specimens [ 5 – 10 ]. In many cancers, gene silencing by promoter methylation seems to be an early event in carcinogenesis and may occur even more frequently than structural inactivation of genes by mutations and deletions [ 11 ].…”

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

“…Promoter methylation of paired like homeodomain 2 ( PITX2 ) transcription factor is a well-established and validated prognostic biomarker in various malignancies, including carcinomas of the prostate, breast, biliary tract, and lung [ 14 – 20 ]. Recent publications suggest a role of methylation status of PITX3 and PITX2 and adjacent long non-coding RNA ( PANCR ) as promising new biomarkers in HNSCC [ 21 , 22 ]. Another gene in this family, the transcription factor PITX1 , might exhibit tumor-suppressing properties by regulating p53 transcription [ 23 ].…”