Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatocellular carcinoma is one of the most lethal cancers worldwide. More accurate stratification of patients at risk is necessary to improve its clinical management. As epithelial-mesenchymal transition is critical for the invasiveness and metastasis of human cancers, we investigated expression profiles of 12 genes related to epithelial-mesenchymal transition through a real-time polymerase chain reaction. From a univariate Cox analysis for a training cohort of 128 hepatocellular carcinoma patients, four candidate genes (E-cadherin [CDH1], inhibitor of DNA binding 2 [ID2], matrix metalloproteinase 9 [MMP9], and transcription factor 3 [TCF3]) with significant prognostic values were selected to develop a risk score of patient survival. Patients with high risk scores calculated from the four-gene signature showed significantly shorter overall survival times. Moreover, the multivariate Cox analysis revealed that four-gene signature (P = 0.0026) and tumor stage (P = 0.0023) were independent prognostic factors for overall survival. Subsequently, the four-gene signature was validated in an independent cohort of 231 patients from three institutions, in which high risk score was significantly correlated with shorter overall survival (P = 0.00011) and disease-free survival (P = 0.00038). When the risk score was entered in a multivariate Cox analysis with tumor stage only, both the risk score (P = 0.0046) and tumor stage (P = 2.6 x 10(-9)) emerged as independent prognostic factors. In conclusion, we suggest that the proposed gene signature may improve the prediction accuracy for survival of hepatocellular carcinoma patients, and complement prognostic assessment based on important clinicopathologic parameters such as tumor stage.
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PMID:Epithelial-mesenchymal transition gene signature to predict clinical outcome of hepatocellular carcinoma. 2033 28

Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease.
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PMID:Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis. 2688 69