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CCR7 enhances TGF-?1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer.

ABSTRACT: CCR7 is a G protein-coupled chemokine receptor. In this study, we used immunohistochemistry with tissue microarrays to measure CCR7 expression in tumor specimens from 122 patients with gastric cancer. We show that CCR7 expression is associated with lymph node metastasis (P = 0.022) and overall survival (OS; P = 0.025), and is an independent factor associated with poorer overall survival (P = 0.032). The CCR7 mechanism was predicted based on bioinformatic analysis and verified in gastric cancer cell lines and primary tumor samples. The data show that CCR7 contributes to TGF-?1-induced epithelial-mesenchymal transition (EMT) and that the effects of TGF-?1 are inhibited by a CCR7 neutralizing antibody or a NF-?B inhibitor. Increased TGF-?1 expression was accompanied by nuclear localization of NF-?B-p65 and higher levels of the mesenchymal marker vimentin in human gastric cancer samples. We conclude that the CCR7 axis mediates TGF-?1-induced EMT via crosstalk with NF-?B signaling, facilitating lymph node metastasis and poorer overall survival in patients with gastric cancer. These findings suggest CCR7 is a novel prognostic indicator and a potential target for gastric cancer therapy.

SUBMITTER: Ma H

PROVIDER: S-EPMC4695190 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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CCR7 enhances TGF-β1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer.

Ma Huiying H Gao Lingling L Li Shichao S Qin Jie J Chen Long L Liu Xinzhou X Xu Pingping P Wang Fei F Xiao Honglei H Zhou Shuang S Gao Qiang Q Liu Binbin B Sun Yihong Y Liang Chunmin C

Oncotarget 20150901 27

CCR7 is a G protein-coupled chemokine receptor. In this study, we used immunohistochemistry with tissue microarrays to measure CCR7 expression in tumor specimens from 122 patients with gastric cancer. We show that CCR7 expression is associated with lymph node metastasis (P = 0.022) and overall survival (OS; P = 0.025), and is an independent factor associated with poorer overall survival (P = 0.032). The CCR7 mechanism was predicted based on bioinformatic analysis and verified in gastric cancer c ...[more]

PMID: 26176983

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Project description:BackgroundThis study aimed to explore whether transforming growth factor β1 (TGF-β1) is correlated with the stiffness of breast lesions and if it can predict axillary lymph node (ALN) metastasis.MethodsA retrospective analysis was performed in our hospital. A total of 135 breast lesions in 130 patients who were to undergo vacuum-assisted excisional biopsy (VAEB) or surgery were enrolled between April 2018 and October 2018. Ultrasound (US) and shear wave elastography (SWE) examinations were performed for every lesion before VAEB or surgery. Pathology results obtained by VAEB or surgery were regarded as gold criteria. The elastic parameters and TGF-β1 expression level of malignant breast lesions were compared with those of benign lesions; the relationship between TGF-β1 expression level in breast lesions and the elastic parameters was analyzed; the TGF-β1 expression level in breast lesions with or without ALN metastasis were compared; and the efficacy of TGF-β1 expression level in predicting ALN metastasis was analyzed.ResultsThe malignant breast lesions were different from benign lesions in the maximum and mean elasticity (Emax, Emean), standard deviation of elasticity (ESD), elastic ratio of the lesions to the peripheral tissue (Eratio), and the occurrence rate of "stiff rim sign" (P<0.001). The expression level of TGF-β1 in benign breast lesions was significantly lower than that in malignant lesions (P<0.001), and the TGF-β1 expression level was positively correlated with Emax, Emean, ESD, and Eratio (r=0.869, 0.840, 0.834, and 0.734, respectively). The expression level of TGF-β1 in breast lesions with or without "stiff rim sign" was significantly different (P<0.001), and the TGF-β1 expression level in malignant breast lesions with ALN metastasis was significantly higher than that in malignant lesions without ALN metastasis (P=0.0009). When TGF-β1 expression level >0.3138 was taken as the cut-off value, its efficacy in predicting ALN metastasis was 0.853, with a sensitivity of 86.67%, and a specificity 83.33%.ConclusionsThe expression level of TGF-β1 was positively correlated with the elastic parameters of breast lesions, and it could be useful for predicting ALN metastasis, especially for negative ALN diagnosis clinically.

Dataset Information

CCR7 enhances TGF-?1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer.

Publications

CCR7 enhances TGF-β1-induced epithelial-mesenchymal transition and is associated with lymph node metastasis and poor overall survival in gastric cancer.

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