Adverse prognosis of epigenetic inactivation in RUNX3 gene at 1p36 in human pancreatic cancer

Abstract

Alteration in transforming growth factor-b signalling pathway is one of the main causes of pancreatic cancer. The human runt-related transcription factor 3 gene (RUNX3) is an important component of this pathway. RUNX3 locus 1p36 is commonly deleted in a variety of human cancers, including pancreatic cancer. Therefore, we examined genetic and epigenetic alterations of RUNX3 in human pancreatic cancer. Thirty-two patients with pancreatic cancer were investigated in this study. We examined the methylation status of RUNX3 promoter region, loss of heterozygosity (LOH) at 1p36, and conducted a mutation analysis. The results were compared with clinicopathological data. Promoter hypermethylation was detected in 20 (62.5%) of 32 pancreatic cancer tissues, confirmed by sequence of bisulphite-treated DNA. Loss of heterozygosity was detected in 11 (34.3%) of 32 pancreatic cancers. In comparison with clinicopathological data, hypermethylation showed a relation with a worse prognosis (P ¼ 0.0143). Hypermethylation and LOH appear to be common mechanisms for inactivation of RUNX3 in pancreatic cancer. Therefore, RUNX3 may be an important tumour suppressor gene related to pancreatic cancer.

Critical regions and spreading of runt-related transcription factor-3 C-phosphate-G (CpG) island methylation in human salivary gland adenoid cystic carcinoma

“…The methylation of the RUNX3 gene is an important mechanism by which RUNX3 protein expression is down-regulated or even lost. The inhibition of RUNX3 expression is correlated with some clinicopathologic parameters, and RUNX3 gene methylation is significantly correlated with tumor development and prognosis [22][23][24][25][26]. Nonetheless, we found no significant relationship between the methylation of the RUNX3 gene CpG island and clinicopathologic parameters, such as sex, age, clinical stage, nerve invasion, lymph node transfer, and metastasis.…”

Unfavorable clinical implications for hypermethylation of RUNX3 in patients with salivary gland adenoid cystic carcinoma

“…It was demonstrated that rUnX3 methylation was significant correlated with clinicopathological parameters, such as clinical stage, nerve invasion, lymph node metastasis and distant metastasis; however, no correlation with gender, age, tumor site and histologic types was noted. these results are consistent with those in the literature which report that 'RUNX3 methylation has significant correlation with tumor progression and prognosis' (12,(51)(52)(53)(54). the degree of rUnX3 methylation in 19 cases of frozen Acc specimens was significantly related with the down-regulation of mRNA and protein of RUNX3, suggesting RUNX3 methylation may be a key mechanism for RUNX3 inactivation in the genesis and progression of Acc.…”

Evaluation of the relationship between dietary factors,CagA-positiveHelicobacter pyloriinfection, andRUNX3promoter hypermethylation in gastric cancer tissue

“…RUNX3 is unique in that it is inactivated primarily by epigenetic silencing, unlike many other tumor suppressors, such as p53, that are inactivated mainly by deletion and mutation [23] . Molecular epidemiology studies have investigated the relationship between DNA hypermethylation-induced inactivation of RUNX3 and individual risk of cancer development in various organs, including the lungs, pancreas, urinary bladder, and gastric cancers [12,[24][25][26] .…”