Publication: Mesane kanseri tanısında kullanılmak üzere üriner protein ve ekzozomal mikro RNA belirteci saptanması
Abstract
Amaç: Üriner ekzozomlarda miRNA ve üriner protein ekspresyonlarının mesane kanserinde biyobelirteç özelliklerinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Mesane kanseri tanısı almış 59 birey ve 34 sağlıklı gönüllü ve 12 takip hastasının idrar örneklerinde ekzozomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p ekspresyonları qRT-PCR; BLCA-4,NMP22, APE1/ Ref1, CRK, VIM protein ekspresyonları ELISA yöntemi ile incelendi.Bulgular: Kas invazyonu gözlenen grupta miR-136-3p eksprese eden örnek yüzdesinin sağlıklı kontrollere göre yüksek olduğu (p=0,0091), en düşük ekzozomal miR-136-3p, miR-139-5p ve miR-19b1-5p ekspresyonun kasa invaze metastatik grupta olduğu belirlendi. Üriner BLCA-4, APE1/ Ref1, CRK ve VIM konsantrasyonlarının mesane kanseri hastalarında sağlıklı kontrollerden yüksek olduğu, miR-136-3p, 139-5p, 19b1-5p ve BLCA4 ile oluşturulmuş modelin %83,5 duyarlılık, %73,5 özgüllük ile kanser kontrol ayrımı yaptığı, miR-136-3p ve BLCA4 ile oluşturulmuş modelin düşük risk grubunu sağlıklı kontrollerden %93,3 duyarlılık, %97,1 özgüllük ile ayırdığı tespit edildi. Sonuçlar: Elde edilen panel sağlıklı kontroller ve mesane kanserlerini (AUC=0,887) ayırmada da düşük riskli hasta grubunu sağlıklı kontrollerden (AUC=0,969) ayırmada da idrar sitolojisine göre üstündür. Ortak belirteçler ile iki ayrımın sağlanması maliyet açısından da avantajlıdır. Yüksek hasta sayısı ile valide edilmesi klinik pratikte kullanımının önünü açabilir.
Title: Identification of urinary protein and exosomal micro RNA markers for the diagnosis of bladder cancer Objective: The aim of this study was to investigate the biomarker properties of urinary exosomal miRNAs and urinary protein concentrations in bladder cancer.Material and Methods: Urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p expressions of 59 bladder cancer patients, 34 healthy volunteers and 12 follow-up patients were examined by qRT-PCR. BLCA-4, NMP22, APE1 / Ref1, CRK and VIM protein expressions in urine were examined by ELISA method.Results: The percentage of miR-136-3p expressing specimens in muscle invasive bladder cancer specimens was higher than in healthy controls (p = 0.0091). The lowest exosomal miR-136-3p, miR-139-5p and miR-19b1-5p expression were detected in the muscle invasive metastatic group. Urinary BLCA-4, APE1 / Ref1, CRK and VIM concentrations were higher in patients with bladder cancer than healthy controls. Logistic regression model consisting of miR-136-3p, 139-5p, 19b1-5p and BLCA4 was differentiated bladder cancer patients from healthy controls with a sensitivity of 83.5% and specificity of 73.5%. miR-136-3p and BLCA4 model was found to differentiate low risk group bladder cancer patients from healthy controls with a sensitivity and specificity of 93.3% and 97.1% respectively.Conclusions: The panel obtained was superior to urine cytology in separating bladder cancers from healthy controls (AUC = 0,887) and low risk patients from healthy controls (AUC = 0,969). It is also advantageous in terms of cost to ensure two distinctions with common markers. Validation with a high number of patients may lead to use in clinical practice.
Title: Identification of urinary protein and exosomal micro RNA markers for the diagnosis of bladder cancer Objective: The aim of this study was to investigate the biomarker properties of urinary exosomal miRNAs and urinary protein concentrations in bladder cancer.Material and Methods: Urine exosomal miR-19b1-5p, 21-5p, 136-3p, 139-5p, 210-3p expressions of 59 bladder cancer patients, 34 healthy volunteers and 12 follow-up patients were examined by qRT-PCR. BLCA-4, NMP22, APE1 / Ref1, CRK and VIM protein expressions in urine were examined by ELISA method.Results: The percentage of miR-136-3p expressing specimens in muscle invasive bladder cancer specimens was higher than in healthy controls (p = 0.0091). The lowest exosomal miR-136-3p, miR-139-5p and miR-19b1-5p expression were detected in the muscle invasive metastatic group. Urinary BLCA-4, APE1 / Ref1, CRK and VIM concentrations were higher in patients with bladder cancer than healthy controls. Logistic regression model consisting of miR-136-3p, 139-5p, 19b1-5p and BLCA4 was differentiated bladder cancer patients from healthy controls with a sensitivity of 83.5% and specificity of 73.5%. miR-136-3p and BLCA4 model was found to differentiate low risk group bladder cancer patients from healthy controls with a sensitivity and specificity of 93.3% and 97.1% respectively.Conclusions: The panel obtained was superior to urine cytology in separating bladder cancers from healthy controls (AUC = 0,887) and low risk patients from healthy controls (AUC = 0,969). It is also advantageous in terms of cost to ensure two distinctions with common markers. Validation with a high number of patients may lead to use in clinical practice.