The Significance Of T-cell Lymphoma Invasion And Metastasis-inducing Factor Over-expression On Prognostic Evaluation Of Gastric Adenocarcinomal

Background:Gastric cancer (GC) comes from the epithelium cells of gastric mucosa, it is the fourth most commonly diagnosed cancer and the second leading cause of cancer deaths worldwide,the most is gastric adenocarcinoma (GAC).Though the morbidity of gastric adenocarcinoma around the world has got down, two-thirds of gastric adenocarcinoma patients are in developing countries, especially in China, Japan and other East Asian countries. The overall prognosis of gastric cancer has gradually improved over the past decades with growing awareness of potential carcinogens, surveillance programs and early diagnosis, as well as advances in surgical techniques and multimodality treatments. Nevertheless, the outcome of advanced stage disease still remains poor with currently available treatments, and a worldwide consensus on the standard management thereof has not been established. To improve prognosis and quality of life in gastric cancer patients, both standardization and individualization of managements are imperative. Despite the significant achievements in the treatment of early GC, the longterm survival rate for advanced GC is still quite low. Metastasis leads to most of the mortalities and has a critical role in the poor prognosis. However, the underlying molecular mechanisms underlying the invasion and metastasis of advanced GC are still poorly understood. Hence, it is urgent to identify important molecules in GC metastasis and progression, which may be used to develop novel avenues for drugs targeting these markers.Tiaml, also called T-cell lymphoma invasion and metastasis-inducing factor, was first identified as a metastasis-related gene in the aggressive mice T lymphoma cells. It is a member of guanine nucleotide exchange factors (GEFs) and regulates the guanosine triphosphatase to facilitate the exchange of guanosine diphosphate for guanosine triphosphate. This indicates that Tiaml is involved many biological processes by regulating a variety of GTP-binding proteins. It has been reported that Tiaml participates in cytoskeleton rearrangement,and cell migration and mobility in T-lymphoma cells, fibroblasts and epithelial cells. Accumulating evidences have shown that Tiaml expression plays a role in cancer progression and metastasis by activating Rho-like GTPases and Tiaml-Racl pathway in various cancers, such as nasopharyngeal carcinoma, breast cancer,colorectal cancer, retinoblastoma hepatocellular carcinoma and Ras-induced skin tumors. Moreover, many studies have shown that Tiaml expression might be a new and independent predictor of prognosis in various solid tumors. However, the potential prognostic relevance of Tiaml expression in gastric adenocarcinoma has no been investigated.Objectives:To explore the expression location of Tiaml protein in gastric adenocarcinoma cell; To investigate the significance of Tiaml protein over-expression on prognostic evaluation of gastric adenocarcinoma.Methods:The localization of the Tiaml protein was determined in the gastric adenocarcinoma cell line using immunofluorescence (IF) staining; Tiaml protein was detected in 102 of GAC,33 of dysplasia and 21 of dysplasia tissues of cancer using immunohistochemical staining method. The correlation between Tiaml over-expression and the prognosis of patients with GAC was also analyzed.Results:Tiaml protein showed a mainly cytoplasmic staining pattern in gastric adenocarcinoma cells, however, then nuclear staining pattern was also observed. The positive rate and strongly positive rate of Tiaml were 85.3%(87/102) and 61.8% (63/102) in GAC, respectively, and both were significantly higher than either in dysplasia or in dysplasia tissues of cancer (both P< 0.01). Tiaml expression was significantly correlated with the differentiation, TNM, LN metastasis, and serosal invasion of GAC (P<0.05), but poor correlated of the patient’s gender, age, and tumor size.Conclusions:Tiaml expression is frequently up-regulated in gastric adenocarcinoma. Tiaml expression level is closely related to the progression and prognosis of GAC. High level of Tiaml expression may partially be used as an important poor prognostic indicator for GAC.