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Association between periostin and epithelial-mesenchymal transition in esophageal squamous cell carcinoma and its clinical significance.

ABSTRACT: The present study aimed to investigate the association between periostin (POSTN), epithelial cadherin (E-cad) and vimentin (Vim) expression levels in esophageal squamous cell carcinoma (ESCC) tissues, and its clinicopathological significance. A total of 58 patients with esophageal cancer were enrolled. Immunohistochemistry was performed to quantify the expression levels of POSTN, E-cad and Vim. E-cad expression was reduced in ESCC tissue, which was associated with severe tumor node metastasis (TNM) stage (P<0.001), lymphatic metastasis (P<0.001) and vascular invasion (P=0.026). Conversely, Vim expression was found to be increased in ESCC tissues, and had associations with TNM stage (P=0.039) and lymphatic metastasis (P=0.039). POSTN overexpression observed in ESCC cells was associated with attenuation of E-cad expression (P<0.001) and elevated expression levels of Vim (P<0.001). Additionally, significant correlations between the overexpression of POSTN in ESCC cells and clinicopathological variables including TNM staging (P=0.009), degree of differentiation (P<0.001), lymphatic metastasis (P=0.009) and vascular invasion (P=0.002) were verified. Multivariate analysis revealed that overexpression of POSTN in ESCC cancer cells is able to predict the poor prognosis of patients independently of overall survival (P=0.022) and disease free survival (P=0.019). The preliminary findings of the present study demonstrate that POSTN is involved in the epithelial-mesenchymal transition of ESCC cells, and may therefore be a predictive factor for tumor invasion and metastasis, as well as an indicator of poor prognosis for patients with ESCC.

SUBMITTER: Lv YJ

PROVIDER: S-EPMC5494835 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Due to its high morbidity and mortality rates, it is urgent to find a molecular target that contributes to esophageal carcinogenesis and progression. In this research, we aimed to investigate the functions of Latent transforming growth factor β binding protein 1(LTBP1) in ESCC progression and elucidate the underlying mechanisms.MethodsThe tandem mass tag-based quantitative proteomic approach was applied to screen the differentially expressed proteins (DEPs) between 3 cases of ESCC tumor samples and paired normal tissues. Then the DEPs were validated in human ESCC tissues using western blot assays and GEPIA database respectively. The expression level of LTBP1 was detected in 152 cases of ESCC tissues and paired normal tissues. Loss-of-function assays were performed to detect the function of LTBP1 in vivo and in vitro. Immunofluorescence and Western blot assays were used to detect the expression of apoptosis, epithelial-mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) markers.ResultsA total of 39 proteins were screened to be up-regulated (ratio > 2.0) in all three ESCC tissues. The results of immunohistochemistry assays indicated that the expression level of LTBP1 was higher in ESCC tissues than that in paired normal tissues (p < 0.001). Overexpression of LTBP1 was positively associated with lymphatic metastasis in ESCC (p = 0.002). Down-regulation of LTBP1 inhibited the invasion and migration as well as metastatic abilities in vitro and in vivo. It was also observed the down-regulation of LTBP1 not only decreased the mesenchymal phenotypes but also inhibited TGFβ-induced EMT in ESCC cells. We further found that down-regulation of LTBP1 enhanced ESCC cells' sensitivity to 5-FU treatment. Inhibition of LTBP1 expression could also attenuate induction of CAFs transformation and restrain fibroblast express fibronectin (FN1) in ESCC cells.ConclusionOverexpression of LTBP1 was associated with lymph node metastasis in ESCC. Our results indicated that LTBP1 not only increased the malignant behaviors of ESCC cells but also induced EMT and CAFs transformation. Our studies suggested an oncogenic role of LTBP1 in ESCC progression and it may serve as a potential therapeutic target for ESCC patients.

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Association between periostin and epithelial-mesenchymal transition in esophageal squamous cell carcinoma and its clinical significance.

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