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

Kamlua,Surasee; Patrakitkomjorn,Siriporn; Jearanaikoon,Patcharee; Menheniott,Trevelyan  R.; Giraud,Andrew  S.; Limpaiboon,Temduang

doi:10.3892/or.2011.1583

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

Authors:
- Surasee Kamlua
- Siriporn Patrakitkomjorn
- Patcharee Jearanaikoon
- Trevelyan R. Menheniott
- Andrew S. Giraud
- Temduang Limpaiboon
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Affiliations: Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
Published online on: December 7, 2011 https://doi.org/10.3892/or.2011.1583
Pages: 1207-1212

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Abstract

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 (∆EX2TFF2), resulting in a stop codon (TAG) at exon 1. The ∆EX2TFF2/wtTFF2 ratio in tumors was significantly higher than in normal tissue (P<0.01). Interestingly, high ∆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.

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