RESUMO
Recent introduction of a learning algorithm for cDNA microarray analysis has permitted to select feature set to accurately distinguish human cancers according to their pathological judgments. Here, we demonstrate that hepatitis B virus-positive hepatocellular carcinoma (HCC) could successfully be identified from non-tumor liver tissues by supervised learning analysis of gene expression profiling. Through learning and cross-validating HCC sample set, we could identify an optimized set of 44 genes to discriminate the status of HCC from non-tumor liver tissues. In an analysis of other blind-tested HCC sample sets, this feature set was found to be statistically significant, indicating the reproducibility of our molecular discrimination approach with the defined genes. One prominent finding was an asymmetrical distribution pattern of expression profiling in HCC, in which the number of down-regulated genes was greater than that of up-regulated genes. In conclusion, the present findings indicate that application of learning algorithm to HCC may establish a reliable feature set of genes to be useful for therapeutic target of HCC, and that the asymmetric expression pattern may emphasize the importance of suppressed genes in HCC.
Assuntos
Carcinoma Hepatocelular/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Neoplasias Hepáticas/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , Humanos , Fígado/virologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Análise de Sequência com Séries de Oligonucleotídeos , Valor Preditivo dos Testes , Reprodutibilidade dos TestesRESUMO
For molecular and cytogenetic studies, two partial bacterial artificial chromosome (BAC) libraries of the garlic cultivar Allium sativum L. 'Danyang' were constructed using high molecular weight (HMW) garlic DNA, the pBAC1-SACB1 vector, and the pIndigoBAC536 vector. The average insert size of the BAC library was about 90 kb. The sequence compositions of the BAC clones were characterized by Southern hybridization with garlic genomic DNA and a repetitive sequence clone of garlic. Two BAC clones with weak signals (thus implying mostly unique sequences), GBC2-5e and GBC2-4d, were selected for FISH analysis. FISH analysis localized the GBC2-5e (approximately 100 kb) BAC clone on the long arm of garlic chromosome 7. The other BAC clone, GBC2-4d (approximately 110 kb), gave rise to discrete FISH signals on a mid-size early metaphase chromosome. The FISH screening with BAC clones proved to be a useful resource for molecular cytogenetic studies of garlic, and will be useful for further mapping and sequencing studies of important genes of this plant.
Assuntos
Cromossomos Artificiais Bacterianos/genética , Cromossomos de Plantas/genética , Alho/genética , Southern Blotting , Eletroforese em Gel de Campo Pulsado , Vetores Genéticos/genética , Hibridização in Situ Fluorescente , Coreia (Geográfico)RESUMO
In an attempt to understand the molecular bases of gastric cancer progression, we have analyzed the differentially expressed genes in gastric cancer by SAGE. Four SAGE cDNA tag libraries were constructed from two sets of gastric cancer and normal tissues and 241,127 tags were obtained. By comparing the tags from cancer and normal tissues, 414 differentially expressed tags, representing 383 genes, were identified in cancer tissues (p = 0.01). Of the 414 tags, 50 tags were previously unidentified and potentially novel genes. Although each gastric cancer tissue revealed more than 200 differentially expressed genes compared to the respective normal tissue, the number of genes with consistent regulation patterns in both cancer tissues was 51: 12 up-regulated and 39 down-regulated genes. The genes that showed consistent regulation patterns included well-known genes such as Trefoil factor 3, RegIV, gastric intrinsic factor, and lactotransferrin as well as a few novel candidates. Interestingly, the expression of several genes, such as osteoglycin, prostate stem cell antigen, and histone deacetylase 3, was variable in the two normal tissues but similar in the cancer tissues. The expression profiles of these genes in normal tissues, possibly due to genetic background, could greatly affect individual sensitivity to cancer development and/or progression. The genes identified in this study will provide useful target genes for diagnosis and molecular treatment of gastric cancer.