The Biomarker Effects Of TIAM1 Protein On The Prognostic Evaluation Of Breast Cancer

Background:Breast cancer is one of the most common malignancies in women worldwide and the second leading cause of cancer death among women. T lymphoma invasion and metastasis 1 (Tiam1) is a potential modifier of tumor occurrence and progression. Recent studies showed that Tiaml has be found to be expressed at high levels in many human tumors, including melanoma, pancreatic cancer, colorectal carcinoma, lung cancer and breast cancer. And high-level expression of Tiaml appears to be associated with many human tumors progression. This study attempted to explore the role of Tiam1 in tumor progression and prognostic evaluation of breast cancer.Objectives:To explore the expression location of Tiaml protein in breast cancer cell, and investigate the biomarker effects of Tiam1 protein on the prognostic evaluation of breast cancer.Materials and methods:The localization of the Tiam1 protein was determined in the MDA-MB-231 breast cancer cell line using immunofluorescence (IF) staining, and a total of 153 breast cancer tissues,67 ductal carcinoma in situ (DCIS) and 63 adjacent non-tumor breast tissues were picked-up for immunohistochemical (IHC) staining of the Tiam1 protein. The correlation between Tiam1 expression and clinicopathological characteristics were evaluated by Chi-square test and Fisher’s exact tests. Disease-free survival (DFS) and 10-year overall survival (OS) rates were calculated by the Kaplan-Meier method. Additionally, univariate and multivariate analyses were also performed by the Cox proportional hazards regression models.Results:1. Tiam1 protein showed a mainly cytoplasmic staining pattern in breast cancer cells, however, then nuclear staining pattern was also observed. The strongly positive rate of Tiaml protein expression was significantly higher in breast cancer (42.5%,65/153) than that in DCIS (40.3%,27/67) and adjacent non-tumor tissues (12.7%,8/63). The strongly positive rate of Tiaml was related with molecular type, tumor stage, Her2 expression and Ki-67 expression. Additionally, survival analyses showed that DFS and 10-year OS rates were significantly higher in breast cancer patients with high-level Tiam1 expression than those with low-level Tiam1 expression. Moreover, univariate analysis suggested that molecular type, clinical stage, Her2 expression levels and Tiaml expression levels were also significantly associated with DFS and 10-year OS rates of breast cancer patients, and multivariate analysis suggested that Tiaml emerged as a significant independent prognostic factor along with tumor stage in patients with breast cancer.2. The apoptotic index showed that 0.25±0.21% in tissues with low Tiaml expression levels and 0.73±0.17% in tissues with high Tiaml expression levels, and it was also showed that there was a significant correlation between the Tiam1 expression levels and the apoptotic index (P< 0.05).Conclusions:Tiaml expression is frequently up-regulated in breast cancer. Tiaml was correlated with clinicopathological parameters and it may be a useful prognostic biomarker and a potential therapeutic target for patients with breast cancer.