Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor progression in pancreatic cancer.
Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor progression in pancreatic cancer.
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Tiam I 表达升高与胰腺癌预后不良相关并促进肿瘤进展
DOI：
10.2147/ott.s171425
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发表时间：
2018
影响因子：
4
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Ding M;Li Y;Yang Y;Zhu K;Che S;Lin Z;Chen L
已知t细胞淋巴瘤侵袭转移诱导因子1 （Tiam1）参与肿瘤进展。然而，其在胰腺导管腺癌（PDAC）中的分子作用和机制尚不清楚。本研究的目的是确定Tiam1在PDAC中的表达水平并探讨其潜在的分子机制。免疫组织化学检测PDAC组织中Tiam1蛋白的表达水平。Western blot和免疫荧光染色证实了Tiam1在胰腺癌细胞中的表达。使用短干扰RNA构建tiam1沉默的PC细胞。随后，我们进行了菌落形成、划伤、迁移和侵袭实验，以探索Tiam1在PC细胞中的分子机制。结果显示，Tiam1在PDAC组织中的表达明显高于配对的非肿瘤组织，且Tiam1过表达与PDAC的组织学分级（P=0.040）和淋巴结转移（P=0.031）显著相关。Tiam1高表达的PDAC患者5年总生存率明显低于Tiam1低表达的PDAC患者。更重要的是，单因素和多因素分析表明，Tiam1表达以及淋巴结转移是PDAC患者重要的独立预后因素。此外，我们还证明了Tiam1的下调与细胞增殖降低、迁移和侵袭能力降低有关。Tiam1的高表达在PDAC的进展中起着重要作用，可能是不良预后的潜在生物标志物和治疗靶点。
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. 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. 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. 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.