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Expression of Jagged1 predicts postoperative clinical outcome of patients with gastric cancer.

ABSTRACT: Clinical significance of Notch1 activation in gastric cancer has been elucidated in our previous study, but the role of its ligands remains obscure. This study aims to evaluate the prognostic value of Jagged1 expression in patients with gastric cancer.We examined Jagged1 expression in tumor and nontumor tissues in retrospectively enrolled 302 patients with gastric cancer undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochemical staining. The Kaplan-Meier method and Cox regression models were used to evaluate the prognostic value of Jagged1 expression and its association with clinicopathological features. We created a predictive nomogram by integrating Jagged1 expression with the TNM staging system for overall survival of gastric cancer patients.Jagged1 expression in gastric cancer was decreased compared with that in nontumor tissues. Low expression of Jagged1 in tumor and nontumor both predicted a dismal outcome. The Jagged1 risk derived from Jagged1 expression in tumor/nontumor tissue gave a further discrimination for the prognosis of gastric cancer patients. By Cox multivariate analysis, the Jagged1 risk was defined as an independent prognostic factor. The generated nomogram performed well in predicting the 3- and 5-year overall survival of gastric cancer patients.Jagged1 is a potential prognostic biomarker for overall survival, which could be integrated with TNM stage to give a better risk stratification for gastric cancer patients.

SUBMITTER: Liu H

PROVIDER: S-EPMC4658849 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Expression of Jagged1 predicts postoperative clinical outcome of patients with gastric cancer.

Liu Hao H Zhang Heng H Shen Zhenbin Z Wang Xuefei X Wang Zhenglin Z Xu Jiejie J Sun Yihong Y

International journal of clinical and experimental medicine 20150915 9

<h4>Background</h4>Clinical significance of Notch1 activation in gastric cancer has been elucidated in our previous study, but the role of its ligands remains obscure. This study aims to evaluate the prognostic value of Jagged1 expression in patients with gastric cancer.<h4>Methods</h4>We examined Jagged1 expression in tumor and nontumor tissues in retrospectively enrolled 302 patients with gastric cancer undergoing gastrectomy at Zhongshan Hospital of Fudan University in 2008 by immunohistochem ...[more]

PMID: 26628960

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Project description:A gene expression signature indicative of activated wound responses is common to more than 90% of non-neoplastic tissues adjacent to breast cancer, but these tissues also exhibit substantial heterogeneity. We hypothesized that gene expression subtypes of breast cancer microenvironment can be defined and that these microenvironment subtypes have clinical relevance.Gene expression was evaluated in 72 patient-derived breast tissue samples adjacent to invasive breast cancer or ductal carcinoma in situ. Unsupervised clustering identified two distinct gene expression subgroups that differed in expression of genes involved in activation of fibrosis, cellular movement, cell adhesion and cell-cell contact. We evaluated the prognostic relevance of extratumoral subtype (comparing the Active group, defined by high expression of fibrosis and cellular movement genes, to the Inactive group, defined by high expression of claudins and other cellular adhesion and cell-cell contact genes) using clinical data. To establish the biological characteristics of these subtypes, gene expression profiles were compared against published and novel tumor and tumor stroma-derived signatures (Twist-related protein 1 (TWIST1) overexpression, transforming growth factor beta (TGF-?)-induced fibroblast activation, breast fibrosis, claudin-low tumor subtype and estrogen response). Histological and immunohistochemical analyses of tissues representing each microenvironment subtype were performed to evaluate protein expression and compositional differences between microenvironment subtypes.Extratumoral Active versus Inactive subtypes were not significantly associated with overall survival among all patients (hazard ratio (HR) = 1.4, 95% CI 0.6 to 2.8, P = 0.337), but there was a strong association with overall survival among estrogen receptor (ER) positive patients (HR = 2.5, 95% CI 0.9 to 6.7, P = 0.062) and hormone-treated patients (HR = 2.6, 95% CI 1.0 to 7.0, P = 0.045). The Active subtype of breast microenvironment is correlated with TWIST-overexpression signatures and shares features of claudin-low breast cancers. The Active subtype was also associated with expression of TGF-? induced fibroblast activation signatures, but there was no significant association between Active/Inactive microenvironment and desmoid type fibrosis or estrogen response gene expression signatures. Consistent with the RNA expression profiles, Active cancer-adjacent tissues exhibited higher density of TWIST nuclear staining, predominantly in epithelium, and no evidence of increased fibrosis.These results document the presence of two distinct subtypes of microenvironment, with Active versus Inactive cancer-adjacent extratumoral microenvironment influencing the aggressiveness and outcome of ER-positive human breast cancers.

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Expression of Jagged1 predicts postoperative clinical outcome of patients with gastric cancer.

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Expression of Jagged1 predicts postoperative clinical outcome of patients with gastric cancer.

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