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Pituitary tumor-transforming 1 increases cell motility and promotes lymph node metastasis in esophageal squamous cell carcinoma.

ABSTRACT: Human pituitary tumor-transforming 1 (PTTG1)/securin is a putative oncoprotein that is overexpressed in various tumor types. However, the involvement of PTTG1 in gastrointestinal cancer development and progression remains unclear. In this study, we investigated the clinical significance and biological effects of PTTG1 in esophageal squamous cell carcinoma (ESCC). Immunohistochemical studies performed on 113 primary ESCC specimens revealed a high prevalence of PTTG1 overexpression (60.2%), which was significantly associated with lymph node metastasis (regional, P = 0.042; distant, P = 0.005), advanced tumor stage (P = 0.028), and poorer overall survival (P = 0.017, log-rank test; P = 0.044, Cox proportional hazard model). Eleven ESCC cell lines expressed PTTG1 protein at levels 2.4 to 6.6 times higher than those in normal esophageal epithelial cells (HEEpiC). PTTG1 protein expression was confined to the nucleus in HEEpiC cells but present in both the cytoplasm and nucleus in ESCC cells. Two small interfering RNAs (siRNA) inhibited PTTG1 mRNA and protein expression in three ESCC cell lines by 77% to 97%. In addition, PTTG1 down-regulation by these siRNAs significantly reduced cell motility in all three ESCC cell lines (P < 0.01) in vitro, as well as popliteal lymph node metastases of ESCC cells in nude mice (P = 0.020). Global gene expression profiling suggested that several members of the Ras and Rho gene families, including RRAS, RHOG, ARHGAP1, and ARHGADIA, represented potential downstream genes in the PTTG1 pathway. Taken together, these findings suggest that PTTG1 overexpression promotes cell motility and lymph node metastasis in ESCC patients, leading to poorer survival. Thus, PTTG1 constitutes a potential biomarker and therapeutic target in ESCCs with lymph node metastases.

SUBMITTER: Ito T

PROVIDER: S-EPMC2988648 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Pituitary tumor-transforming 1 increases cell motility and promotes lymph node metastasis in esophageal squamous cell carcinoma.

Ito Tetsuo T Shimada Yutaka Y Kan Takatsugu T David Stefan S Cheng Yulan Y Mori Yuriko Y Agarwal Rachana R Paun Bogdan B Jin Zhe Z Olaru Alexandru A Hamilton James P JP Yang Jian J Abraham John M JM Meltzer Stephen J SJ Sato Fumiaki F

Cancer research 20080501 9

Human pituitary tumor-transforming 1 (PTTG1)/securin is a putative oncoprotein that is overexpressed in various tumor types. However, the involvement of PTTG1 in gastrointestinal cancer development and progression remains unclear. In this study, we investigated the clinical significance and biological effects of PTTG1 in esophageal squamous cell carcinoma (ESCC). Immunohistochemical studies performed on 113 primary ESCC specimens revealed a high prevalence of PTTG1 overexpression (60.2%), which ...[more]

PMID: 18451147

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Project description:PurposeTo investigate the value of radiomics models based on CT at different phases (non-contrast-enhanced and contrast-enhanced images) in predicting lymph node (LN) metastasis in esophageal squamous cell carcinoma (ESCC).Methods and materialsTwo hundred and seventy-four eligible patients with ESCC were divided into a training set (n =193) and a validation set (n =81). The least absolute shrinkage and selection operator algorithm (LASSO) was used to select radiomics features. The predictive models were constructed with radiomics features and clinical factors through multivariate logistic regression analysis. The predictive performance and clinical application value of the models were evaluated by area under receiver operating characteristic curve (AUC) and decision curve analysis (DCA). The Delong Test was used to evaluate the differences in AUC among models.ResultsSixteen and eighteen features were respectively selected from non-contrast-enhanced CT (NECT) and contrast-enhanced CT (CECT) images. The model established using only clinical factors (Model 1) has an AUC value of 0.655 (95%CI 0.552-0.759) with a sensitivity of 0.585, a specificity of 0.725 and an accuracy of 0.654. The models contained clinical factors with radiomics features of NECT or/and CECT (Model 2,3,4) have significantly improved prediction performance. The values of AUC of Model 2,3,4 were 0.766, 0.811 and 0.809, respectively. It also achieved a great AUC of 0.800 in the model built with only radiomics features derived from NECT and CECT (Model 5). DCA suggested the potential clinical benefit of model prediction of LN metastasis of ESCC. A comparison of the receiver operating characteristic (ROC) curves using the Delong test indicated that Models 2, 3, 4, and 5 were superior to Model 1(P< 0.05), and no difference was found among Model 2, 3, 4 and Model 5(P > 0.05).ConclusionRadiomics models based on CT at different phases could accurately predict the lymph node metastasis in patients with ESCC, and their predictive efficiency was better than the clinical model based on tumor size criteria. NECT-based radiomics model could be a reasonable option for ESCC patients due to its lower price and availability for renal failure or allergic patients.

Dataset Information

Pituitary tumor-transforming 1 increases cell motility and promotes lymph node metastasis in esophageal squamous cell carcinoma.

Publications

Pituitary tumor-transforming 1 increases cell motility and promotes lymph node metastasis in esophageal squamous cell carcinoma.

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