Kim, Young-WonYun, Seok JoongJeong, PhilduKim, Seon-KyuKim, Seon-YoungYan, ChunriSeo, Sung PhilLee, Sang KeunKim, JayoungKim, Wun-Jae2015-09-012015Kim, Young-Won, Seok Joong Yun, Phildu Jeong, Seon-Kyu Kim, Seon-Young Kim, Chunri Yan, Sung Phil Seo, Sang Keun Lee, Jayoung Kim, and Wun-Jae Kim. 2015. “The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.” PLoS ONE 10 (7): e0134552. doi:10.1371/journal.pone.0134552. http://dx.doi.org/10.1371/journal.pone.0134552.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:21462133Previous 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.en-USJournal Article2015-09-0110.1371/journal.pone.0134552