Prognostic role of fgfr3 expression status and tumor-related micrornas level in association with pd-l1 expression in primary luminal non-muscular invasive bladder carcinoma

Background: Bladder cancer is one of the most common urinary tract malignancies. Establishment of robust predictors of disease progression and outcome is important for personalizing treatment of non-muscular invasive bladder carcinoma (NMIBC). In this study we evaluated association of PD-L1 expression with other prognostic biomarkers, such as expression of miRNA-145 and miRNA-200a, FGFR3 gene expression, and mutation status in tissue specimens of the luminal subtype of newly diagnosed high and low grade NMIBC. Methods: Twenty patients with primary luminal NMIBC were enrolled in the study. Tumor grade and risk level were determined in accordance with European Organization for Research and Treatment of Cancer (EORTC) guidelines and World Health Organization (WHO) classification. Neoplasm molecular subtype and PD-L1 expression level were assessed by immunohistochemistry. We used real-time PCR to evaluate the expression of microRNAs and FGFR3. We detected FGFR3 hotspot mutations in codons 248 and 249 by Sanger sequencing. Results: High grade primary luminal NMIBC showed comparatively higher expression of PD-L1 and microRNA-145 than a low grade tumor, whereas the latter had a higher FGFR3 expression and hotspot mutation rate. The tumor grade (HR = 571.72 [11.03-2.96] p = 0.002), PD-L1 expression (HR = 2.33 [0.92-1.92] p = 0.012), and FGFR3 expression (HR = 0.08 [0.17-0.42] p = 0.003) were associated with relapse-free survival. Conclusions: Tumor grade in association with PD-L1 and FGFR3 expression can be considered as a complex predictor for primary luminal NMIBC progression. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Blinova E.1 , Buzdin A.2, 3 , Enikeev D.1 , Roshchin D.4 , Suntsova M.2 , Samyshina E.5 , Drobyshe A.2 , Deryabina O.6 , Demura T.1 , Blinov D.5 , Shic E.1 , Barakat H. 7 , Borger P.8 , Merinov D.4 , Kachmazov A.4 , Serebrianyi S.4 , Tumutolova O.6 , Potoldykova N.1 , Zhdanov P.1 , Grigoryan V.1 , Perepechin D.4
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  • 1 Department of Clinical Anatomy and Operative Surgery, Department of Pathological Anatomy, Institute for Urology and Reproductive Health, Sechenov University, Moscow, 119991, Russian Federation
  • 2 Laboratory of Bioinformatics, Institute for Personalized Medicine, Sechenov University, Moscow, 119991, Russian Federation
  • 3 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russian Federation
  • 4 Russian National Research Center of Radiology, Department of Oncological Urology, Moscow, 125284, Russian Federation
  • 5 All-Union Research Center for Biological Active Compounds Safety, Laboratory of Molecular Pharmacology and Drug Design, Staraja Kupavna, 142450, Russian Federation
  • 6 Laboratory of Pharmacology, Department of Oncology, National Research Ogarev Mordovia State University, Saransk, 430005, Russian Federation
  • 7 Peoples’ Friendship University of Russia
  • 8 Laboratory of the Swiss Hepato-Pancreato-Biliary and Transplantation Center, Department of Surgery, University Hospital Zürich, Zürich, 8091, Switzerland
Cancer progression; Expression; Fibroblast growth factor receptor 3; MicroRNA; Mutation; Non-muscular invasive bladder carcinoma; PD-L1; Prognosis; Tumor relapse
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