DNA/RNA‐based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high‐resolution proteomics analysis by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype‐specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low‐risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross‐omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value.
Introduction: We assessed the pathological characteristics of the radical prostatectomy specimen, the rate of biochemical failure and the functional outcome after surgery, in terms of incontinence and erectile dysfunction rate, in patients on statin medication. Materials and Methods: A total of 588 patients with a mean age 65.2 years (SD = 5.7 years) participated in the study. All patients were contacted and interviewed. Results: Users who had been on statin medication for more than 2 years had lower levels of preoperative serum PSA (p = 0.034), a 2.76 times greater likelihood of being staged as pT3a to pT3b rather than pT2a to pT2c, and a 5.39 times greater likelihood of having a postoperative Gleason score equal to seven or more. Positive surgical margins and urinary incontinence were not significantly associated with statin use. The probability of erectile dysfunction was significantly greater for statin users. Conclusion: Statin medication was associated with a statistically significantly lower PSA value and an increased rate of high Gleason score and pathologic stage in patients receiving medication for more than 2 years. Statins were found to be an independent predictor of recurrence. Lastly, statin users were more likely to present with preoperative and postoperative erectile dysfunction.
ObjectivesTo evaluate the impact of distal ureter management on oncological results after open nephroureterectomy (ONU) comparing transurethral resection of the intramural ureter to conventional open excision, as controversy still exists about the method of choice for managing the distal ureter and bladder cuff during ONU.Patients and methodsWe retrospectively collected data from 378 patients who underwent ONU for upper urinary tract transitional cell carcinoma (UUT-TCC) from 1988 to 2009. Patients were divided into two subgroups according to the type of operation performed. Group A comprised 192 patients who had ONU with open resection of the bladder cuff from 1988 to 1997. Group B comprised 186 patients in whom transurethral resection of the intramural ureter plus single incision ONU was performed between 1998 and 2009. The mean operative time, hospital stay, duration of catheterisation, bladder recurrence rates, and cancer-specific survival (CSS) were assessed.ResultsThe total operative time was statistically significantly less in the endoscopic group (Group B). For catheterisation, patients treated with an open approach (Group A) had a statistically significantly shorter duration of postoperative catheterisation. There was no statistical difference between Groups A and B for the bladder recurrence rate (Group A 24% vs 27% in Group B, P = 0.51). There was no difference in CSS at the 5-year follow-up.ConclusionsONU with transurethral resection of the intramural ureter up to the extravesical fat followed by ureter extraction is an oncologically safe and technically feasible operation.
The SNP rs6983267 is an established marker for a range of cancers. In prostate cancer, it indicates an enhanced risk for carriers to develop the disease in general. In our study it showed no association with aggressive forms or familial and early-onset prostate cancer families.
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