Mp45-17 Clinical Significance of Pd-l1 Protein Expression and Tumor Infiltrating Lymphocytes in Early Stage Urothelial Bladder Carcinomas
Year: 2016
Type: article
Study design: Observational Study
Abstract: and renal pelvis cancers is cystoscopy and urine cytology.Considering the invasiveness and diagnostic performance of the method as well as the highly recurrent nature of urothelial cancers, new non-invasive biomarkers with higher sensitivity are in need.Exosomes and microvesicles (EMV) are released into urine from all the area of nephrons, therefore considered as a promising biomarker source for kidney diseases.When we analyzed urinary EMV mRNA profile, we detected not only kidney specific genes but also bladder specific genes, suggesting that urinary EMV may be useful to detect urothelial diseases as well.Since the urothelial cancers are directly in contact with urine, we hypothesized urinary EMV might show early molecular signatures of urothelial cancers comparing to the currently available urinary cell or protein biomarkers.METHODS: First, RNA-seq analysis of urine samples from urothelial cancer patients (N¼6) was conducted in comparison with healthy and disease controls (N¼6) in order to screen urothelial cancer biomarkers.Furthermore, 104 differentially expressed genes (68 upregulated and 26 down-regulated genes) were identified to detect and distinguish urothelial cancers by locations, grades and stages.Among the differentially expressed genes in urinary EMV, 38 genes were further validated by RT-qPCR in 150 patient urine samples (bladder cancer (N¼102), other urothelial cancer (N¼20), non-urothelial cancer (N¼3), urothelial cancer remission (N¼16), and non-cancer control (N¼9) as well as healthy volunteer urine (N¼9).RESULTS: Unsupervised clustering analysis of urinary EMV mRNA profiles clearly showed different clusters indicating healthy control, bladder cancer, renal pelvis cancer, mild and advanced urothelial cancers.Next, we confirmed that SLC2A1, GAPDH, CRH, GPRC5A, KRT17, P4HA1, ACTB, RNF39, S100A13 and SLC2A3 were not only differentially expressed in the urothelial cancer urine samples in comparison with the cancer remission and disease control samples but also were able to detect non-muscle invasive early stage urothelial cancer with high specificity and sensitivity (AUC 0.749 -0.901 for pT1 bladder cancer).CONCLUSIONS: Since the data are highly correlated with urine cytology results, these urinary EMV mRNA are promising non-invasive biomarkers of urothelial cancer.
Source: The Journal of Urology
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2312727320