Reduced Expression of TFF1 and Increased Expression of TFF3 in Gastric Cancer: Correlation with Clinicopathological Parameters and Prognosis

Abstract

Objectives: The trefoil factor family (TFF) is composed of three thermostable, and protease-resistant proteins, named TFF1, TFF2 and TFF3, and plays a role in gastrointestinal mucosal defence and repair. Recently, TFFs have been found to be related to the development of various types of cancer. This study assessed the relationship between the expression of TFF1 and TFF3 and the clinicopathological parameters in gastric carcinoma (GC). Materials and Methods: The expression of TFF1 and TFF3 was analyzed by immunohistochemistry in 292 GCs and 20 normal gastric tissues. Results: All normal gastric tissues expressed TFF1, but 53.8% of GCs showed reduced TFF1 expression. However, TFF3 was not detected in normal gastric tissues and 44.2% of GCs showed a high level of expression. Highly expressed TFF3 was significantly correlated with lymph node metastasis, lymphatic invasion, vein invasion, and advanced stage. The overall survival was shorter in patients with high expression of TFF3 than in those with low expression of TFF3 in 292 GCs and in 125 early GCs (EGCs). Moreover, in patients with EGCs, high expression of TFF3, associated with reduced expression of TFF1, was determined as an independent poor prognostic marker. Conclusions: Reduced expression of TFF1 and increased expression of TFF3 may play a role in the carcinogenesis of gastric cancer. Furthermore, high expression of TFF3 with reduced expression of TFF1 may be a marker of poor prognosis for patients with EGC.

Immunohistochemistry in Undifferentiated Neoplasm/Tumor of Uncertain Origin

“…194 The expression of TFF1 has been reported to be decreased in carcinomas of the stomach and esophagus when compared with normal mucosa. 193,195 In contrast, TFF1 expression in breast cancer is markedly increased. Our recent studies [83][84][85] demonstrated that TFF1 was overexpressed in breast carcinomas and colorectal ADCs; under- expressed in lung ADCs, ovarian carcinomas, and endometrial carcinomas; and was usually absent in germ cell carcinomas, RCCs, and thyroid carcinomas.…”

Trefoil factors: Gastrointestinal-specific proteins associated with gastric cancer

“…Accumulating evidences manifest that TFF3 may be a causal connection between inflammation and occurrence of GI tumors [24,44,[49][50][51] . A large number of reports have also shown that TFF3 is involved in larger tumor size, tumor cell scattering, angiogenesis, lymph node metastasis, invasion, advanced stage and recurrence [24,[52][53][54][55][56][57][58]. On the contrary, anti-sense TFF3 inhibits cell growth and significantly enhances the apoptosis induced by adriamycin in human GC [59].…”

Analysis of a Urinary Biomarker Panel for Incident Kidney Disease and Clinical Outcomes

“…Pathologic expression of TFF-3 has been observed in several cancers, including endometrial and prostate adenocarcinoma, gastric cancer, and several lung cancer histologic subtypes. [26][27][28] Although there has been considerable focus on the cardiovascular consequences of kidney disease, the importance of non-CVD outcomes as a cause of death in CKD is increasingly recognized. People with CKD experience premature morbidity and death from a wide range of causes compared with age-matched members of the general population.…”