Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases

Radical perineal prostatectomy and early continence: outcomes after 120 cases

PURPOSE: Evaluate the results of urinary continence on patients who had undergone radical perineal prostatectomy (RPP) for clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed the continence data of 120 patients with pathology of cT1-cT2N0M0 prostate cancer and who had undergone RPP. Continence was assessed on the day of catheter removal, at the end of the first and third month, and the first year postoperatively. The patients who were continent immediately after catheter removal were classified in the group of “immediately continent” while the patients who became continent during the 3 postoperative months were classified as “early continent.” RESULTS: Mean duration of catheterization was 10 (10-25) days. Of 120 patients, 44 (36.7%) were immediately continent. At the end of the first and third months, 65 (54.1%) and 87 (72.5%), respectively, were early continent. At the one-year follow-up, 95.3% of 107 cases whose one-year follow-up data were available were continent. When the relationship between patients’ age and continence was analyzed, it was found that the early continence rates were 77.7% (7/9), 73.3% (33/45), 73.4% (36/49), and 64.7% (11/17) in the groups of = 49, 50-59, 60-69, and = 70 years, respectively (p = 0.68). CONCLUSIONS: The majority of patients who underwent RPP rapidly regained continence within 3 months. RPP is an exceptional alternative approach for radical surgery in the treatment of localized prostate cancer