Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand.
Oncol Rep. 2012 Apr;27(4):1207-12. doi: 10.3892/or.2011.1583. Epub 2011 Dec 7.
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.
三叶因子 2（TFF2）是三叶因子家族的成员，在许多癌症中过度表达，包括胆管癌（CCA）。大多数研究都集中在野生型 TFF2（wtTFF2）表达上，但关于 TFF2 mRNA 可变剪接变异体的信息尚未报道。在这项研究中，我们旨在鉴定和定量胆管癌（CCA）中的新型 TFF2 剪接变异体。使用定量逆转录聚合酶链反应（QRT-PCR），对 78 个肿瘤和 15 个正常相邻组织中 TFF2 剪接变异体相对于野生型（wt）TFF2 mRNA 的表达进行了定量。分析了 TFF2 剪接变异体与 wtTFF2 的比值与临床参数的相关性。我们发现了一种新型的 TFF2 剪接变异体，外显子 2 跳跃（∆EX2TFF2），导致外显子 1 出现终止密码子（TAG）。肿瘤中的 ∆EX2TFF2/wtTFF2 比值明显高于正常组织（P<0.01）。有趣的是，与低比值相比，高 ∆EX2TFF2/wtTFF2 比值与良好的预后显著相关（P=0.017）。相比之下，wtTFF2 蛋白的存在与 CCA 患者的生存不良相关（P=0.034）。这是首例报道三叶因子剪接变异体及其作为 CCA 预后生物标志物的潜在应用。
