Identification of prognostic biomarkers in plasma of patients with metastatic urothelial carcinoma (mUC).

Patrik Palacka 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute; Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia info_outline Patrik Palacka, Eliska Svastova, Lucia Csaderova, Michal Chovanec, Katarina Rejlekova, Jana Obertova, Peter Lesko, Zuzana Orszaghova, Valentina De Angelis, Jan Slopovsky, Andrea Holickova, Jan Roska, Eveline Orasova, Boris Nociar, Michal Mego, Jozef Mardiak, Miroslav Chovanec

Authors Patrik Palacka 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute; Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia info_outline Patrik Palacka, Eliska Svastova, Lucia Csaderova, Michal Chovanec, Katarina Rejlekova, Jana Obertova, Peter Lesko, Zuzana Orszaghova, Valentina De Angelis, Jan Slopovsky, Andrea Holickova, Jan Roska, Eveline Orasova, Boris Nociar, Michal Mego, Jozef Mardiak, Miroslav Chovanec Organizations 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute; Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia, Biomedical Research Center, Institute of Virology, Department of Cancer Biology, Slovak Academy of Sciences, Bratislava, Slovakia, 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia, Cancer Research Institute, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia, National Cancer Institute, Bratislava, Slovakia Abstract Disclosures Research Funding Other This research was funded by grant of the Integrated Infrastructure Operational Program, ITMS: 313011AFG5, co-financed by the European Regional Development Fund & OncoReSearch, Slovakia. Background: Performance status and visceral metastasis before first-line chemotherapy based on cisplatin (CDDP) predict survival of subjects with mUC. The objective of this study was to explore the prognostic value of selected plasma biomarkers. Methods: We have evaluated the samples from 86 mUC subjects (64.0% males). Performance status of ECOG 2 and visceral metastasis were present in 39.5% and 50.0% cases, respectively. The MILLIPLEX panels were used for determination of 51 biomarkers in plasma taken from patients before systemic therapy initiation. Study population was dichotomized into high and low groups by median for each parameter. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was carried out by the Cox regression model. Results: At median follow-up of 8.6 months (6.4-10.1), 95.3% of patients experienced disease progression and died. Better PFS was associated with low levels of nine biomarkers: IL-1RA (HR 0.65, P=0.0425), IL-6 (HR 0.52, P=0.002), IL-8 (HR 0.46, P=0.0002), IL-10 (HR 0.49, P=0.0004), IL-15 (HR 0.61, P=0.0198), IL-22 (HR 0.45, P=0.0043), MCP-1 (HR 0.59, P=0.0147), M-CSF (HR 0.59, P=0.0119), and VEGF-A (HR 0.64, P=0.0392). OS was significantly better in patients with low levels of G-CSF (HR 0.42, P=0.047), IL-1RA (HR 0.63, P=0.0314), IL-2 (HR 0.61, P=0.0249), IL-6 (HR 0.47, P=0.004), IL-8 (HR 0.44, P=0.0001), IL-10 (HR 0.43, P<0.0001), IL-15 (HR 0.53, P=0.0026), IL-22 (HR 0.47, P=0.0065), IL-27 (HR 0.63, P=0.0343), MCP-1 (HR 0.59, P=0.0134), M-CSF (HR 0.55, P=0.0042), TNFα (HR 0.53, P=0.0024), and VEGF-A (HR 0.59, P=0.0124). The independent prognostic values of IL-6, IL-10, MCP-1, M-CSF, and TNFα were confirmed in a multivariate analysis. Conclusions: In this study, we have proved that selected plasma biomarkers may have a prognostic value in mUC patients. Further research is required to understand their role as the biomarkers, but also potentially treatable pathogenic factors for mUC development. This research was funded by grant of the Integrated Infrastructure Operational Program, ITMS: 313011AFG5, co-financed by the European Regional Development Fund & OncoReSearch, Slovakia.