Project description:We identified the molecular subtypes and conserved modules in gastric cancer by unsupervised clustering algorithm. We defined five molecular subtypes and six molecular signatrues of gastric cancer associated with the biological heterogeneity of gastric cancer and clinical outcome of patients.
Project description:We identified the molecular subtypes and conserved modules in gastric cancer by unsupervised clustering algorithm. We defined five molecular subtypes and six molecular signatrues of gastric cancer associated with the biological heterogeneity of gastric cancer and clinical outcome of patients.
Project description:Clinical heterogeneity of gastric cancer reflected in unequal outcome of treatment is poorly defined in molecular level, and molecular subtypes and their associated biomarkers have not been established to improve prognostification and treatment of gastric cancer. Using microarray technologies, we analyzed gene expression profiling data from patients with advanced gastric cancer and uncovered potential prognostic subtypes and identify gene expression signature associated with prognosis. Using microarray technologies, we analyzed gene expression profiling data from patients with advanced gastric cancer and uncovered potential prognostic subtypes and identify gene expression signature associated with prognosis.
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
Project description:Molecular analysis of gastric cancer identifies discrete subtypes associated with distinct clinical characteristics and survival outcomes: the ACRG (Asian Cancer Research Group) study [gastric tumors]