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

Characteristics of Susac syndrome: a review of all reported cases

In Susac syndrome, occlusions of microvessels-presumed to be mediated by an autoimmune response to an as yet unknown antigen--lead to a characteristic clinical triad of CNS dysfunction, branch retinal artery occlusions, and sensorineural hearing impairment. Susac syndrome is considered a rare but important differential diagnosis in numerous neurological, psychiatric, ophthalmological, and ear, nose and throat disorders. Improved understanding of this disorder is crucial, therefore, to ensure that patients receive appropriate treatment and care. Current knowledge on Susac syndrome is largely based on reports of single patients, small case series, and nonsystematic reviews. The aim of this Review is to extend these previous, primarily anecdotal findings by compiling data from all 304 cases of Susac syndrome that have been published worldwide, which were identified following a literature search with predefined search, inclusion and exclusion criteria. From this data, we present an overview of demographic, clinical and diagnostic data on Susac syndrome, providing a reliable basis for our current understanding of this rare disease. Where possible, we make recommendations for clinical diagnosis, differential diagnosis, and management of patients with suspected Susac syndrome

The Liver Prometastatic Reaction of Cancer Patients: Implications for Microenvironment-Dependent Colon Cancer Gene Regulation

Colon cancer frequently metastasizes to the liver but the genetic and phenotypic properties of specific cancer cells able to implant and grow in this organ have not yet been established. The contribution of the patient’s genetic, physiologic and pathologic backgrounds to the incidence and development of hepatic colon cancer metastases is also presently misunderstood. At a transcriptional level, hepatic metastasis development is in part associated with marked changes in gene expression of colon cancer cells that may originate in the primary tumor. Other changes occur in the liver and are regulated by hepatic cells, which represent the new microenvironment for metastatic colon cancer cells. However, hepatic parenchymal and non-parenchymal cell functions are also affected by both tumor-derived factors and systemic host factors, which suggests that the hepatic metastasis microenvironment is a functional linkage between the hepatic pathophysiology of the colon cancer patient and the biology of its cancer cells. Therefore, together with metastasis-related gene profiles suggesting the existence of liver metastasis potential in primary tumors, new biomarkers of the prometastatic microenvironment supported by the liver reaction to colon cancer factors may be helpful for the individual assessment of hepatic metastasis risk in colon cancer patients. In addition, knowledge on hepatic metastasis gene regulation by the hepatic microenvironment may open multiple opportunities for therapeutic intervention during colon cancer metastasis at both subclinical and advanced stages