RESUMO
Expression profiling has demonstrated that transcriptomes of primary malignancies differ from those in normal tissue. It is unknown, however, whether there exist "surrogate" transcriptional markers in peripheral blood mononuclear cells (PBMCs) of patients with solid tumors. We identified transcripts expressed differentially between PBMCs from renal cell carcinoma patients and normal subjects, some of which appear to reflect specific immune responses of circulating cells. We also identified small sets of predictor genes distinguishing PBMCs from renal cell carcinoma patients and normal volunteers with high accuracy. The present findings have important implications for diagnosis and future clinical pharmacogenomic studies of antitumor therapies.
Assuntos
Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/genética , Neoplasias Renais/sangue , Neoplasias Renais/genética , Leucócitos Mononucleares/fisiologia , Adulto , Idoso , Carcinoma de Células Renais/classificação , Feminino , Perfilação da Expressão Gênica , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/genética , Neoplasias Renais/classificação , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/biossíntese , RNA Mensageiro/sangue , RNA Mensageiro/genética , Transcrição GênicaRESUMO
Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. Currently, diagnosis of RA may take several weeks, and factors used to predict a poor prognosis are not always reliable. Gene expression in RA may consist of a unique signature. Gene expression analysis has been applied to synovial tissue to define molecularly distinct forms of RA; however, expression analysis of tissue taken from a synovial joint is invasive and clinically impractical. Recent studies have demonstrated that unique gene expression changes can be identified in peripheral blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis, and lupus. To identify RA disease-related genes, we performed a global gene expression analysis. RNA from PBMCs of 9 RA patients and 13 normal volunteers was analyzed on an oligonucleotide array. Compared with normal PBMCs, 330 transcripts were differentially expressed in RA. The differentially regulated genes belong to diverse functional classes and include genes involved in calcium binding, chaperones, cytokines, transcription, translation, signal transduction, extracellular matrix, integral to plasma membrane, integral to intracellular membrane, mitochondrial, ribosomal, structural, enzymes, and proteases. A k-nearest neighbor analysis identified 29 transcripts that were preferentially expressed in RA. Ten genes with increased expression in RA PBMCs compared with controls mapped to a RA susceptibility locus, 6p21.3. These results suggest that analysis of RA PBMCs at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment.