Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas

Abstract

This study identifies the genetic fingerprint of poorly differentiated endometrioid endometrial carcinomas (G3-EEC) and analyses the potential utility of trefoil factor 3 (TFF3) as novel serum marker in G3-EEC. Affymetrix microarrays were used to identify the gene expression patterns of 19 snap-frozen G3-EEC and 15 normal endometrium (NE) biopsies. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to validate TFF3 expression. Finally, TFF3 serum levels were determined by ELISA in 25 G3-EEC patients, 42 healthy controls, and in 13 endometrial hyperplasia patients. Hierarchical cluster analysis showed TFF3 as the top differentially expressed gene between 363 upregulated genes in G3-EEC, when compared with NE. Trefoil factor 3 gene expression levels analysed by qRT-PCR significantly correlated with Affymetrix results (Po0.001; rs ¼ 0.85). By immunohistochemistry, TFF3 protein was significatively more expressed in EEC compared with NE (Po0.01), with cytoplasmatic positivity in 79% G3-EEC and 18% NE. Patients harbouring G3-EECs had significantly higher TFF3 serum concentration by ELISA when compared with healthy patients (Po0.001) or patients harbouring endometrial hyperplasia (P ¼ 0.012). In conclusion, TFF3 is highly expressed at gene and protein level in G3-EEC. Further investigations on a wider set of samples are warranted to validate TFF3 as a novel serum marker for early detection and/or monitoring of G3-EEC patients.

The combination of serum trefoil factor 3 and pepsinogen testing is a valid non-endoscopic biomarker for predicting the presence of gastric cancer: a new marker for gastric cancer risk

“…Interestingly, recent studies demonstrated that serum TFF3 levels were increased in patients with high-grade endometrial cancer [18], and in patients with advanced prostate cancer [19], and TFF3 was overexpressed in the tissues of these cancers [18,20]. Further studies are required to elucidate the mechanism of the linkage between TFF3 and gastric cancer or other types of cancers.…”

Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer

“…Moreover, serum TFF3 levels in lung, pancreatic, endometrial and advanced prostate cancer patients are up-regulated significantly [42,75,95,96]. Therefore, increased serum TFF3 levels may not be specific for GC.…”

Serum Trefoil Factor 3 as a Protein Biomarker for the Diagnosis of Colorectal Cancer

“…Several studies have reported that serum levels of TFF are significantly increased in patients with cancer (mainly gastric cancer) and thus serve as a potential biomarker for cancer screening. [13][14][15][16] Therefore, we conducted this study to determine the serum levels of TFF3 in patients with CRC and assess the diagnostic accuracy of serum TFF3. The diagnostic accuracy was further analyzed in comparison with the serum CEA level.…”