Yeh et al. BMC Cancer 2011, 11:139 http://www.biomedcentral.com/1471-2407/11/139 Page 10 of 12 Figure 7 Prognostic significance of co-expression of c-Met and Axl or PDGFR-a in human bladder cancer patients. Kaplan-Meier survival analysis revealed that co-expression of c-Met/Axl (A) or c-Met/PDGFR-a (B) is significantly associated with poor survival in bladder cancer patients than those with single-receptor-positive or no receptor expression (p = 0.021 & 0.049, respectively). imperative to clarify the significance of Axl and/or PDGFR-a as an additional biomarker or implementation of MEK1/2 inhibitor in the design of c-Met-targeting therapy for human bladder cancer patients. It is interesting to note that induction of Axl via ‘’kinase switching’’ confers the Gleevec resistance in relapsed patients with c-Kit- or PDGFR-a-driven tumors of the gastrointestinal tract [48]. Therefore, evaluation of RTK expression profile in human cancer may provide signaling network information and help in prediction of potential drug resistance [49]. Olaussen et al. showed that combinations of tyrosine kinase inhibitors could induce a synergistic antitumor effect and thus improve the therapeutic efficacy [50]. When more highly selective or multi-target tyrosin kinase inhibitors become avail- able, the discovery of co-expression of RTKs in cancer cells highlights the necessity for individualized therapies in the future. Additional material Additional file 1: c-Met expression in NIH/3T3 and NIH-Met5 cell lines in the presence or absence of Tet and/or HGF. The cells and the treatment is the same as Figure 1A, except the expression of IgG was shown as the loading control. M: protein marker. Additional file 2: The relationship among c-Met, Sp1, Axl and PDGFR-a demonstrated by c-Met siRNA. NIH-Met5 cells (1 × 106/plate) were transfected with c-Met siRNA (250 nM and 500 nM) for 24 h. Then, cells were harvested and total protein was extracted and analyzed for c- Met, Sp1, Axl and PDGFR-a expression by Western blotting. b-actin was used as the internal control. The numbers under each band represent the relative intensity. Acknowledgements This project was supported by grants of Landmark Project Grant A25 of the National Cheng Kung University funded by the Ministry of Education in Taiwan, 96-2628-B-006-003-MY3 from the National Science Council; and NHRI-EX99-9930BI from the National Health Research Institutes, Taiwan. We thank Dr. R. Zuchini for critical reviewing this manuscript. Author details 1Department of microbiology and immunology, College of medicine, National Cheng Kung University, Tainan, Taiwan. 2Department of pathology, College of medicine, National Cheng Kung University, Tainan, Taiwan. 3Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan. 4Department of parasitology, College of medicine, National Cheng Kung University, Tainan, Taiwan. 5Department of computer science and information engineering, National Cheng Kung University, Tainan, Taiwan. 6Center for gene regulation and signal transduction research, National Cheng Kung University, Tainan, Taiwan. 7Graduate Institute of Medical Informatics, Taipei Medical University, Taipei, Taiwan. 8Department of Urology, Chia-Yi Christian Hospital, Chia-Yi, Taiwan. Authors’ contributions CYT, SMS, and HHY participated in conceptualization, carried out this study, and drafted the manuscript; JWS, YCL, JHC, SMT, GR and TYC participated in the microarray data collection and analysis; CHS and NHC provided the clinical specimens; NHC and HSL conceived of the study, and participated in its design and coordination. All authors read and approved the final manuscript Competing interests The authors declare that they have no competing interests. Received: 25 May 2010 Accepted: 16 April 2011 Published: 16 April 2011