Expression of inflammasome-related genes in bladder cancer and their association with cytokeratin 20 messenger RNA.
BACKGROUND
Inflammation plays a crucial role in different stages of cancer development and has long been associated with various types of cancer. Strong associations between dysregulated inflammasome activity and human heritable and acquired inflammatory diseases highlight the importance of this pathway in the immune response. The inflammasome is a large complex of NOD-like receptors called NLRs and drives growth and progression of different tumors. The aim of the present study was the characterization of some NLR genes, NLRP3, NLRP4, NLRP9, and NAIP, in urine sediment of patients with bladder cancer. Cytokeratin 20 and survivin were used as confirmed markers of bladder cancer.


METHODS
For this study, 3 groups of subjects were considered: patients harboring bladder cancer, subjects affected by bladder inflammation (CTR1), and healthy subjects (CTR0). Total RNA was extracted from urine sediments and resulting complementary DNA was used for amplification by real-time polymerase chain reaction. Results were stratified according to tumor stage, grade, and risk of progression and recurrence.


RESULTS
The expression of cytokeratin 20 was always significantly higher in patients with bladder cancer when compared with that in both the tumor-free groups. NLRP3, NLRP4, NLRP9, and NAIP were overexpressed in patients with BCa when compared with that in CTR0. Stratification according to tumor stage, grade, and risk of recurrence and progression showed NLRP up-regulations in patients with early-stage cancer. NAIP was overexpressed in high-risk patients in comparison to CTR0 and in high-grade patients compared with CTR0 and CTR1.


CONCLUSIONS
These data are relevant to demonstrate the role of inflammasome in urothelial carcinoma, making NLR genes in urine sediment potential candidates for bladder cancer diagnosis.
Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Italy.
Giulia
G
Poli
Department of Experimental Medicine-Section of Terni, University of Perugia, Italy.
Stefano
S
Brancorsini
Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Italy.
Giovanni
G
Cochetti
Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Italy.
Francesco
F
Barillaro
Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Italy. Electronic address: mariagiuliaegidi@gmail.com.
Maria Giulia
MG
Egidi
Department of Surgical and Biomedical Sciences, Institute of Urological, Andrological Surgery and Minimally Invasive Techniques, University of Perugia, Italy.
Ettore
E
Mearini
D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053554:Keratin-20 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D058847:Inflammasomes; D053554:Keratin-20; D012333:RNA, Messenger
Bladder cancer; Cytokeratin; Gene expression; Inflammasome