Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor progression in pancreatic cancer
Authors Ding MN, Li Y, Yang Y, Zhu K, Che SL, Lin ZH, Chen LY
Received 17 April 2018
Accepted for publication 12 June 2018
Published 26 July 2018 Volume 2018:11 Pages 4367—4375
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Yao Dai
Mina Ding,1 Yue Li,1 Yang Yang,2 Kun Zhu,1 Shuanlong Che,2 Zhenhua Lin,2,3 Liyan Chen1,3
1Department of Biochemistry and Molecular Biology, Yanbian University Medical College, Yanji 133002, China; 2Department of Pathology and Cancer Research Center, Yanbian University Medical College, Yanji 133002, China; 3Department of Jilin Province, Key Laboratory of the Science and Technology, Yanji 133002, China
Objective: T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) is known to be involved in tumor progression. However, its molecular roles and mechanism in pancreatic ductal adenocarcinoma (PDAC) remain unclear. The purpose of this study is to determine Tiam1 expression levels and investigate its underlying molecular mechanism in PDAC.
Materials and methods: Tiam1 protein expression levels in PDAC tissues were examined using immunohistochemistry. Tiam1 expression was confirmed in pancreatic cancer (PC) cells by Western blot and immunofluorescence staining. Tiam1-silenced PC cells were created using short interfering RNA. Subsequently, colony formation, scratch, and migration and invasion assays were carried out to explore the molecular mechanisms of Tiam1 in PC cells.
Results: The results indicated that Tiam1 expression was significantly higher in PDAC tissues than in paired non-tumor tissues, and overexpression of Tiam1 was significantly correlated with histological grade (P=0.040) and lymph node metastasis (P=0.031) in PDAC. The PDAC patients with high Tiam1 expression had significantly lower 5-year overall survival than patients with low Tiam1 expression. More importantly, univariate and multivariate analysis suggested that Tiam1 expression, along with lymph node metastasis, is a significant independent prognostic factor for patients with PDAC. Furthermore, we also demonstrated that the downregulation of Tiam1 was associated with decreased cell proliferation and reduced migratory and invasive capability.
Conclusion: High expression of Tiam1 plays a significant role in the progression of PDAC and may be a potential biomarker of poor prognosis as well as a therapeutic target.
Keywords: Tiam1, pancreatic cancer, prognosis, survival analysis, carcinogenesis
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