RESUMO
BACKGROUND: Our objective was to examine how the gene expression profile of tumor tissue correlates with lymph node metastasis in patients with advanced colorectal adenocarcinoma (CRAC). METHODS: We studied 36 patients (20 men and 16 women, 22-90 years of age) treated for CRAC (classifications of T2, T3, or T4; histological grade of G1 or G2). Amplified tumor mRNA samples were exposed to 20,000 human sequence probes and digitized images of the hybridized samples were analyzed. RESULTS: On average, 2389 probes were detected above the background, with an average correlation R value of 0.19 between data from different patient groups (with or without lymph node invasion, colon or rectal, with or without angio-lymphatic invasion, with or without recurrence). Lymph node metastasis had a statistically significant signature according to Significance Analysis of Microarrays (SAM) and parametric t-tests, with a false discovery rate (FDR)=0.1% and p=0.001, respectively. Cross-correlation of these two tests identified 102 transcripts as being potentially related to node metastases, with fold changes in the range of 2.182-12.960. CONCLUSION: We identified 102 differentially expressed genes related to the presence of lymph node metastases in patients with advanced colorectal cancer.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , Metástase Linfática/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Genes que codificam proteínas envolvidas na biossíntese, na ação e na metabolização dos esteróides sexuais são polimórficos. Essa condição poderia explicar as variações individuais na densidade mamográfica. Avaliaram-se 115 mulheres pós-menopáusicas não-usuárias de terapia hormonal e sem lesões mamárias clínica ou mamograficamente indentificadas. Todas se submeteram à mamografia bilateral e determinou-se densidade radiológica por três observadores independentes, tomando-se como base a classificação dos padrões mamográficos do ACR-BIRADS®, 2003 (duas avaliações subjetivas e uma computadorizada ferramenta de histograma de escala de cinza do software Adobe Photoshop® 7.0). Obtiveram-se amostras de raspado bucal para extração de DNA, que foi realizada segundo protocolo do Kit GFX®, da Amersham-Pharmacia, para células bucais. Após a extração do DNA, realizou-se PCR-RFLP (Reação de Cadeia Polimerase Restriction Fragment Length Polymorphism) para análise dos polimorfismos presentes no íntron (HaeIII e Xbal) e éxon 1 (MspI e PvuII) do gene do Reα. Houve alto grau de concordância entre os três observadores na determinação da densidade mamográfica. Trinta e quatro mulheres tinham mamas densas e 81, mamas lipossubstituídas. Não houve associação significativa entre os polimorfismos HaeIII e PvuII com a densidade mamográfica. Porém, essa mesma relação com os polimorfismos MspI e XbaI revelou tendência ao significado estatístico.
Genes that encode proteins involved in the biosynthesis, action and metabolism of sexual steroids are polymorphics. This condition could explain the individual variations in mammographic density. A hundred and fifteen postmenopausal women, notin use of hormonal therapy and without clinical or mammographic lesions were assessed.Three independent observers classified mammography density pattern considering the ACR-BIRADS®2003(two subjective assessments and one objective assessment - software Adobe Photoshop 7.0). Oral swabs (Cytobrush) were obtained to extract DNA, following the Kit GFX ® from Amersham-Pharmacia protocol to oral cells. After DNA extraction, PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) was performed to analyze the presence of polymorphisms in intron 1 (HaeIII and Xbal) and exon 1 (MspI and PvuII) from estrogen receptor gene. There was a good agreement among the tree observers with regard to mammographic density. Thirty four women had dense breasts and eighty one had non dense breast. Estrogen receptor gene polymorphisms HaeIII and PvuII showed no association with mammographic density, while this association between estrogen receptor gene polymorphisms Mspl and Xbal showed near the significance.
