A novel TFF2 splice variant (ΔEX2TFF2) correlates with longer overall survival time in cholangiocarcinoma

Trefoil factor 2 (TFF2) is a member of trefoil factor family found to beoverexpressed in many cancers including cholangiocarcinoma (CCA). The majorityof studies have focused on wild-type TFF2 (wtTFF2) expression, but informationregarding alternative splicing variants of TFF2 mRNA has not been reported. Inthis 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 forthe expression of the TFF2 splice variant relative to wild-type (wt) TFF2 mRNAusing quantitative reverse transcriptase polymerase chain reaction (QRT-PCR).The ratio of TFF2 splice variant against wtTFF2 was analyzed for associationswith clinical parameters. We found a novel TFF2 splice variant, exon 2 skipping(∆EX2TFF2), resulting in a stop codon (TAG) at exon 1. The ∆EX2TFF2/wtTFF2 ratioin tumors was significantly higher than in normal tissue (P<0.01). Interestingly,high ∆EX2TFF2/wtTFF2 ratio was significantly associated with good prognosis comparedwith low ratio (P=0.017). In contrast, the presence of wtTFF2 protein was associatedwith poor survival of CCA patients (P=0.034). This is the first report of a trefoilfactor splice variant and its potential application as a prognostic biomarkerin CCA.