Molecular Signature Analysis: the Potential of gene-expression Analysis in Cardiomyopathy

Abstract

Despite the expanding knowledge base of the molecular and cellular pathophysiology and management of cardiomyopathy, it still remains difficult to accurately distinguish between patients who will someday develop circulatory collapse and require cardiac transplantation from those with excellent long-term prognosis. Of equal importance, current medical practice does not include strategies to tailor therapies to patients most likely to benefit, while at the same time seeking predictors of poor or adverse responsiveness. Gene-expression analysis using microarray technology, by providing a phenotypic resolution not possible with standard clinical criteria, has enormous potential to provide better information regarding prognosis and response to therapy in heart-failure patients. Emerging data demonstrate that a molecular signature can accurately identify etiology in cardiomyopathy, supporting ongoing efforts to identify expression profiling-based biomarkers, although microarray research in cardiomyopathy is still in its earliest stages. The ultimate potential application of transcriptome-based molecular signature analysis is individualization of the management of heart-failure patients, whereby a patient with a newly diagnosed cardiomyopathy could, through molecular signature analysis, be offered an accurate assessment of prognosis, and how individualized medical therapy could affect his or her outcome.

Keywords::

• cardiomyopathy
• gene expression
• microarray
• molecular signature analysis
• prognosis

Acknowledegments

Research supported by National Institutes of Health Grant 5RO1-HL-065455. Joshua M Hare is a recipient of a Paul Beeson Physician Faculty Scholars in Aging Research Award. Michelle M Kittleson is a recipient of the Pearl M Stetler Research Fund for Women Physicians Fellowship Award.