Prognostic and predictive biomarkers in early stage non-small cell lung cancer: Tumor based approaches including gene signatures

In early stage non-small cell lung cancer (NSCLC) large randomized trials have demonstrated that in patients with radically resected disease adjuvant chemotherapy improves 5-year survival rates. However, a customization of systemic treatment is needed to avoid treatments in patients cured by surgery alone or to justify the use of adjuvant chemotherapy in high risk patients, including those in stage IA. Recently, the possibility of identifying prognostic and predictive factors related to the genetic signatures of the tumor that could affect adjuvant and neo-adjuvant treatment choices for resectable non-small cell lung cancer (NSCLC) has been of interest. This review summarizes the current status and future opportunities for clinical application of genotyping and genomic tests in early NSCLC

Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation

Steroidogenic Factor-1 (SF-1) is a nuclear receptor that has a pivotal role in the development of adrenal glands and gonads and in the control of steroid hormone production, being also implicated in the pathogenesis of adrenocortical tumors. We have analyzed the mechanisms how SF-1 controls gene expression in adrenocortical cells and showed that it regulates different categories of genes according to its dosage. Significant correlations exist between the localization of SF-1-binding sites in chromatin under different dosage conditions and dosage-dependent regulation of gene expression. Our study revealed unexpected functional interactions between SF-1 and Neuron-Restrictive Silencer Factor/RE1-Silencing Transcription Factor (NRSF/REST), which was first characterized as a repressor of neuronal gene expression in non-neuronal tissues, in the regulation of gene expression in steroidogenic cells. When overexpressed, SF-1 reshapes the repertoire of NRSF/REST—regulated genes, relieving repression of key steroidogenic genes. These data show that NRSF/REST has a novel function in regulating gene expression in steroidogenic cells and suggest that it may have a broad role in regulating tissue-specific gene expression programs