The regulation of gene expression profiles in clear cell renal cell carcinoma by tumor heterogeneity and environmental exposure.

摘要

Currently, the disease management and therapeutic strategies for renal cell carcinoma (RCC) have arisen from cancer biology discoveries, but have evolved fairly independently of individual tumor biology. Thus, a gap has emerged in our understanding of the fundamental paradigms of what core molecular features are important for tissue based biomarker research today. Although extensive effort has been placed on identifying molecular biomarkers for RCC, remarkably, there are few validated biomarkers with substantive impact on managing disease prognosis. The emergence of high-throughput molecular profiling technologies provides the opportunity to explore the underlying molecular features of RCC that will warrant the enhanced understanding of its biology and shed light on future therapeutic methods to treat the disease.;Identifying molecular biomarkers that provide insight towards biological processes, pathogenesis, and response to therapeutics has been at the forefront of current research. The cancer biology field has focused especially on this area in hopes of further understanding the molecular aberrations that contribute to disease development and progression. Prognostic biomarkers are also needed for making personalized treatment decisions, particularly at a time when adjuvant and neoadjuvant options are becoming the mainstay of therapy for many cancers, including Renal Cell Carcinoma (RCC). Exploiting the genome to uncover biomarkers that are indicative of disease progression and aggressiveness can improve patient treatment and survival.;In this dissertation, novel gene expression signatures for the predominant subtype of RCC, clear cell Renal Cell Carcinoma (ccRCC), are validated as imperative prognostic signatures, whose underlying biology is driven by distinct metabolic pathways. Furthermore, environmental exposures to the heavy metal Cadmium, alters the kidney genome and epigenome that may influence the kidney to develop into these ccRCC subtypes and thus impact patient prognosis. These biomarkers of ccRCC have the potential to have an impression on the clinical arena and can be used for assessing prognostic and predictive outcomes.