S9-Fibronectin, EGF-R, HB-EGF:biomarkers of urothelial damage during intravesical adjuvant therapy?

Risultato della ricerca: Other


Intravesical chemotherapy and immunotherapy with BCG represent the standard therapy toprevent recurrence after transurethral resection (TUR) of non-muscle invasive bladder cancer (NMI-BC).Maintenance for at least one year is considered the best regimen. Noteworthy, a relevant number ofpatients do not complete the planned treatment due to local toxicity of the drug given intravesically1, 2. Amajor challenge for the urologists is to identify an early urothelial damage biomarker to prevent severelocal toxicity requiring treatment interruption and to improve patient's compliance. The preliminarypurpose of our research was to verify the possible correlation between urothelial damage induced byintravesical treatment and the expression of potential biomarkers in urine or bladder washing solution.Fibronectin (FN), Epidermal Growth Factor-Receptor (EGF-R) and Heparin-binding Epidermal GrowthFactor-like Growth Factor (HB-EGF) have been preliminary investigated. The urinary HB-EGF expression inpatients with interstitial cystitis has been already analyzed by some studies3, 4, 5 The biomarkers trendduring therapy with hyaluronic acid and chondroitin sulphate solution will be investigated.Materials and Methods: we collected 50 ml urine and bladder washing solution during intravesicaltherapy in 55 patients after NMI-BC TUR and in 10 healty controls for a total of 200 samples. Aftercentrifugation, total cellular RNA was isolated from the cell pellett using miRNeasy Mini Kit (Qiagen®)according to the manufacturer's instructions. We investigated FN and EGF-R gene expression by Real Timequantitative PCR. Finally, the abundance of HB-EGF in urine samples was measured using Enzyme-linkedimmunosorbent assay (ELISA) (Abcam®) following manufacturer's instructions.Results: The FN gene expression levels in NMI-BC compared with controls were increased 4.7 fold whileEGF-R levels were decreased 0.9 fold. In the patients in whom local toxicity due to intravesical therapy wasclinically relevant, the FN gene expression levels were increased 5.82 fold, and the EGF-R one wasdecreased 0.88 fold. In contrast patients before starting therapy or with a good tolerance showed geneexpression levels increased 1.9 fold for FN and 1.1 fold for EGF-R. In patients receiving hyaluronic acid andchondroitin sulphate solution to treat the severe vesical toxicity the average FN gene expression levelswere decreased from 3 to 0.6 fold, with concomitant symptomatic improvement. HB-EGF protein levels inurine in patients receiving intravesical chemo or immunotherapy were increased 1.2 fold compared tocontrols and remained unchanged during therapy. No fold change was detected in patients treated withhyaluronic acid and chondroitin sulphate solution. Our preliminary data will be updated in the finalpresentation. Statistical analysis is ongoing.Conclusion: EGF-R gene expression in the bladder washing solution and HB-EGF levels in urine did notshow significant fold change in relation to urothelial damage compared to controls. Preliminarly, FN geneexpression in bladder washing solution showed an overexpression during urothelial damage and decreaseafter therapy with hyaluronic acid and chondroitin sulphate solution in correlation to symptoms relief.
Lingua originaleEnglish
Numero di pagine2
Stato di pubblicazionePublished - 2013


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