Evaluation of promoter hypomethylation and expression of p73 as a diagnostic and prognostic biomarker in Wilms' tumour.

AIMS

A member of the p53 family, the p73 gene is essential for the maintenance of genomic stability, DNA repair and apoptosis regulation. This study was designed to evaluate the utility of expression and DNA methylation patterns of the p73 gene in the early diagnosis and prognosis of Wilms' tumour (WT).

METHODS

Methylation-specific PCR, semi-quantitative (sq-PCR), real-time quantitative PCR (qRT-PCR), receiver operating characteristic (ROC), and survival and hazard function curve analyses were utilised to measure the expression and DNA methylation patterns of p73 in WT tissue samples with a view to assessing diagnostic and prognostic value.

RESULTS

The relative expression of p73 mRNA was higher, while the promoter methylation level was lower in the WT than the control group (p<0.05) and closely associated with poor survival prognosis in children with WT (p<0.05). Increased expression and decreased methylation of p73 were correlated with increasing tumour size, clinical stage and unfavourable histological differentiation (p<0.05). ROC curve analysis showed areas under the curve of 0.544 for methylation and 0.939 for expression in WT venous blood, indicating the higher diagnostic yield of preoperative p73 expression.

CONCLUSIONS

Preoperative venous blood p73 level serves as an underlying biomarker for the early diagnosis of WT. p73 overexpression and concomitantly decreased promoter methylation are significantly associated with poor survival in children with WT.