Novel Potential Biomarkers Associated With Epithelial to Mesenchymal Transition and Bladder Cancer Prognosis Identified by Integrated Bioinformatic Analysis

To provide tables that allow urologists to easily calculate a superficial bladder cancer patient's short- and long-term risks of recurrence and progression after transurethral resection. A combined analysis was carried out of individual patient data from 2596 superficial bladder cancer patients included in seven European Organization for Research and Treatment of Cancer trials. A simple scoring system was derived based on six clinical and pathological factors: number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and grade. The probabilities of recurrence and progression at one year ranged from 15% to 61% and from less than 1% to 17%, respectively. At five years, the probabilities of recurrence and progression ranged from 31% to 78% and from less than 1% to 45%. With these probabilities, the urologist can discuss the different options with the patient to determine the most appropriate treatment and frequency of follow-up.

Weighted gene coexpression network analysis (WGCNA) is a powerful 'guilt-by-association'-based method to extract coexpressed groups of genes from large heterogeneous messenger RNA expression data sets. We have utilized WGCNA to identify 11 coregulated gene clusters across 2342 breast cancer samples from 13 microarray-based gene expression studies. A number of these transcriptional modules were found to be correlated to clinicopathological variables (e.g. tumor grade), survival endpoints for breast cancer as a whole (disease-free survival, distant disease-free survival and overall survival) and also its molecular subtypes (luminal A, luminal B, HER2+ and basal-like). Examples of findings arising from this work include the identification of a cluster of proliferation-related genes that when upregulated correlated to increased tumor grade and were associated with poor survival in general. The prognostic potential of novel genes, for example, ubiquitin-conjugating enzyme E2S (UBE2S) within this group was confirmed in an independent data set. In addition, gene clusters were also associated with survival for breast cancer molecular subtypes including a cluster of genes that was found to correlate with prognosis exclusively for basal-like breast cancer. The upregulation of several single genes within this coexpression cluster, for example, the potassium channel, subfamily K, member 5 (KCNK5) was associated with poor outcome for the basal-like molecular subtype. We have developed an online database to allow user-friendly access to the coexpression patterns and the survival analysis outputs uncovered in this study (available at http://glados.ucd.ie/Coexpression/).

The aim of this paper was to conduct a critical systematic review of the available literature on the clinical and economic burden of bladder cancer in developed countries, with a focus on the cost effectiveness of interventions aimed at reducing that burden.Forty-four economic studies were included in the review. Because of long- term survival and the need for lifelong routine monitoring and treatment, the cost per patient of bladder cancer from diagnosis to death is the highest of all cancers, ranging from 96000-187000 US dollars (2001 values) in the US. Overall, bladder cancer is the fifth most expensive cancer in terms of total medical care expenditures, accounting for almost 3.7 billion US dollars (2001 values) in direct costs in the US. Screening for bladder cancer in the general population is currently not recommended. The economic value of relatively new and less expensive urine assays and molecular urinary tumour markers has not been assessed. However, the literature suggests that screening patients suspected of having bladder cancer and using less invasive diagnostic procedures is cost effective. Very few cost-effectiveness studies have evaluated intravesical therapies such as bacillus Calmette-Guérin and mitomycin in the management of superficial disease and no robust recommendations can be drawn. Economic analyses suggest that non-surgical treatment strategies for the management of invasive disease aiming at bladder preservation may not be cost effective, because they have not consistently demonstrated survival benefits and do not eliminate the need for subsequent radical cystectomy. The literature suggests that the current conventional frequent follow-up and monitoring of patients can be cost effectively replaced by less frequent and less invasive monitoring, and should rely more heavily on intravesical chemotherapy to reduce the need for cystoscopies. Bladder cancer is a fairly common and costly malignancy. Nevertheless, the existing literature only contributes marginally to our knowledge concerning the burden of bladder cancer and the economic value of various interventions. The limited value of the literature in this area may be attributed to (i) being published as abstracts rather than full peer-reviewed evaluations; (ii) employing questionable methodologies; and (iii) being in many cases nearly obsolete, rendering them less relevant to, if not in conflict with, current clinical practice. Consequently, opportunities exist to conduct meaningful economic research in all areas of the management of bladder cancer, including screening, diagnosis, follow-up and treatment, especially with respect to new and innovative pharmaceutical and other technologies.