Molecular Biomarkers & Diagnosis

A biomarker, or biological marker, is in general a substance used as an indicator of a biological state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Biomarkers play an essential role in much disease detection. Much kind of biomarkers are available in the field of medical science with lots of positive as well as negative effect. Biomarkers will become one of the major driving forces of pharmaceutical research and drug development in the coming years. A specific and ideal biomarker for many unbeaten disease like cancer is still a big challenge.

Lung cancer, even early stage disease, is an important cause of cancer related death in the US. The Warburg Effect, a phenomenon first described by Otto Warburg, occurs when tumor cells utilize glucose through glycolysis even in the presence of adequate oxygen (aerobic glycolysis). Previously described markers of the Warburg effect and altered tumor metabolism include hypoxia inducible factor 1 (HIF-1), pyruvate dehydrogenase kinase 1 (PDK-1), mammalian target of rapamycin (mTOR), carbonic anhydrase 9 (CA-9), hexokinase 2 (HK-2), and phosphorylated AMP-activated protein kinase (pAMPK). The presence of these antigens was assessed in peripheral and central regions of 58 resected stage I non-small cell lung carcinomas by tissue microarray (TMA) and immunohistochemistry (IHC). Using the median staining intensity as a cut off between high and low expression, peripheral and central antigen expression was correlated with overall and recurrence free survival in univariate and multivariate analysis. In our study population high levels of HIF-1? in peripheral tumor regions were associated with worse overall and recurrence free survival. Central tumor expression of HIF-1? did not significantly correlate with outcome. A similar trend in the peripheral tumor was seen with PDK-1. In contrast, high levels of mTOR in central tumor cells were associated with improved overall survival. These findings suggest features of the Warburg effect even in early stage (small) lung tumors. Furthermore, they highlight the importance of assessing metabolic markers in the context of oxygen tension and tumor microenvironment. The significance of high HIF-1? expression may be different in relatively oxygenated tumor periphery than it is in the cells of more hypoxic tumor center.

MicroRNAs (miRNA) are small non-coding RNAs that regulate gene expression post-transcriptionally. They bind to complementary sequences on target mRNA and typically down regulate expression or increase the rate of degradation; however, the roles of miRNA are still evolving and some miRNA have been shown to increase specific gene translation. miRNA holds a unique position among RNA for use as a biomarker due to its unique stability. Unlike mRNA, miRNA has been shown to be remarkably stable in a variety of tissues and body fluids. This greatly facilitates the use of miRNAs as clinical biomarkers of disease and injury since sample handling and processing is much less problematic when compared to mRNA. miRNA expression profiles have been extensively investigated for distinguishing cancerous vs. non-cancerous tissue. Taking this approach one step further, profiles of miRNA in cell-free body fluids have also been able to distinguish patients with different types of cancer and even provide prognostic information about disease outcome. The rationale behind this approach is that cancerous masses release miRNA into the systemic circulation and changes in the pattern and amount of miRNA can be used to detect the type of cancer. A recent extension of this approach is using miRNA in cell-free body fluids to detect organ injury. Several studies have shown increased serum levels of specific miRNA after myocardial or hepatocellular injury. Since some miRNA exhibit tissue specific expression, it is possible that miRNA profiles could be used to not only identify gross organ injury but also distinguish between different types of organ injury (e.g., heart vs. liver). This article will provide an overview of the role of miRNA in the cell, review the literature on using miRNA profiles to identify organ injury, and highlight the potential use of miRNA for assessing drug-induced liver injury. It should be noted that at the time of this writing, none of the profiles have been qualified for clinical use by the FDA.

The objective of the study was to develop a model for the diagnosis of prion diseases in live animals, using magnetic resonance imaging (MRI). Hamsters experimentally infected with the 263K strain of scrapie were imaged periodically during the course of prion infection. Changes in the brain, particularly the hippocampus, were observed during the first quarter of the incubation period. These changes included an increase in T2 relaxation time and apparent diffusion coefficient (ADC), indicative of an increase in the water content of tissues. These changes were apparent well before the appearance of clinical symptoms, and did not correlate with the typical histological changes characteristic of prion disease, (vacuolation, accumulation of PrP protein, gliosis) suggesting that the changes are caused by a progressive accumulation of fluid. This oedema may be a novel early marker of prion disease, and could play a role in pathogenesis.