A novel TFF2 splice variant (Delta EX2TFF2) correlates with longer overall survival time in cholangiocarcinoma

作者：Kamlua Surasee; Patrakitkomjorn Siri****; Jearanaikoon Patcharee; Menheniott Trevelyan R; Giraud Andrew S; Limpaiboon Temduang^*

来源：Oncology Reports, 2012, 27(4): 1207-1212.

DOI：10.3892/or.2011.1583

• cholangiocarcinoma
• trefoil factor 2
• alternative splicing mRNA
• biomarker

Trefoil factor 2 (TFF2) is a member of trefoil factor family found to be overexpressed in many cancers including cholangiocarcinoma (CCA). The majority of studies have focused on wild-type TFF2 (wtTFF2) expression, but information regarding alternative splicing variants of TFF2 mRNA has not been reported. In this study, we aimed to identify and quantify a novel TFF2 splice variant in cholangiocarcinoma (CCA). Seventy-eight tumors and 15 normal adjacent tissues were quantified for the expression of the TFF2 splice variant relative to wild-type (wt) TFF2 mRNA using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). The ratio of TFF2 splice variant against wtTFF2 was analyzed for associations with clinical parameters. We found a novel TFF2 splice variant, exon 2 skipping (Delta EX2TFF2), resulting in a stop codon (TAG) at exon I. The Delta EX2TFF2/wtTFF2 ratio in tumors was significantly higher than in normal tissue (P<0.01). Interestingly, high Delta EX2TFF2/wtTFF2 ratio was significantly associated with good prognosis compared with low ratio (P=0.017). In contrast, the presence of wtTFF2 protein was associated with poor survival of CCA patients (P=0.034). This is the first report of a trefoil factor splice variant and its potential application as a prognostic biomarker in CCA.

• 出版日期2012-4