title: The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.
abstract: Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Young-Won
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Seok Joong
authors.initials: SJ
authors.lastname: Yun
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Phildu
authors.initials: P
authors.lastname: Jeong
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; Korean Bioinformation Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Seon-Kyu
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea; Department of Functional Genomics, University of Science and Technology, Daejeon, Korea.
authors.forename: Seon-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Chunri
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Sung Phil
authors.initials: SP
authors.lastname: Seo
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Sang Keun
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Surgery, Harvard Medical School, Boston, MA, United States of America; Departments of Surgery and Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, United States of America.
authors.forename: Jayoung
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; C550706:PDGFRL protein, human; D025521:Tumor Suppressor Proteins; D019859:Proto-Oncogene Proteins c-met; D017479:Receptors, Platelet-Derived Growth Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D002945:Cisplatin