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

Life

Ekaterina Blinova¹  Evgenia Shich¹  Dmitry Enikeev¹  Vagarshak Grigoryan¹  Pavel Zhdanov¹  Tatiana Demura¹  Natalia Potoldykova¹  Dmitrij Perepechin²  Aleksandr Kachmazov²  Dmitry Roshchin²  Dmitrij Merinov²  Stanislav Serebrianyi²  Oxana Tumutolova³  Olga Deryabina³  Haydar Barakat⁴  Maria Suntsova⁵  Aleksey Drobyshev⁵  Anton Buzdin⁵  Elena Samyshina⁶  Dmitry Blinov⁶  Pieter Borger⁷ 

[1] Department of Clinical Anatomy and Operative Surgery, Department of Pathological Anatomy, Institute for Urology and Reproductive Health, Sechenov University, 119991 Moscow, Russia;Department of Oncological Urology, Russian National Research Center of Radiology, 125284 Moscow, Russia;Department of Oncology, Laboratory of Pharmacology, National Research Ogarev Mordovia State University, 430005 Saransk, Russia;Department of Propaedeutics of Dental Diseases, People’s Friendship University of Russia, 117198 Moscow, Russia;Laboratory of Bioinformatics, Institute for Personalized Medicine, Sechenov University, 119991 Moscow, Russia;Laboratory of Molecular Pharmacology and Drug Design, All-Union Research Center for Biological Active Compounds Safety, 142450 Staraja Kupavna, Russia;Laboratory of the Swiss Hepato-Pancreato-Biliary and Transplantation Center, Department of Surgery, University Hospital Zürich, 8091 Zurich, Switzerland;

关键词: non-muscular invasive bladder carcinoma;    fibroblast growth factor receptor 3;    mutation;    prognosis;    cancer progression;    PD-L1;   

DOI  :  10.3390/life10110305

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown