Project description:In CRC, 1) to identify epigenetic changes at inter-tumor and intra-tumor level, and 2) to relate intra-tumor clonality to clinical, molecular and histopathologic parameters. From 79 FFPE tumors, 3 different regions were macrodissected: invasive front (IF), digestive tract surface (DTS) and central bulk (CB). Clinical, molecular, and histopathologic parameters were stablished. Epigenetic analysis was performed using Infinium 450K beadchip (Illumina) and R statistics. Intra-tumor regions clustered together by patient. The biggest epigenetic changes were in IF vs DTS/CB. By patient, the most often divergent region was IF (49.4%) comparing with DTS and CB (25.3% in both). It did not correlate with histopathologic, molecular and clinical parameters.Epigenetic clonality is higher at intra-tumor level. The highest changes are observed in IF vs DTS/CB. No association with histopathologic, molecular, and clinical characteristics was found. SNP characterization of 9 patients of teh discovery cohort were hibridized on Infinium HumanOncoArray-500 v1 beadchip, to asses the genetic clonality of the samples among the three intratumoral regions studied.
2016-08-16 | GSE81362 | GEO
Project description:CulturedMeat Colorrectal Cancer 16S
Project description:immunotherapy offers a better prognosis for pancreatic cancer patients. As a direct extension of this work, various new therapy methods that are under exploration and clinical trials could be assessed or evaluated using the newly developed mathematical prognosis model.
Project description:The present data suggest that the infiltration of inactive CD8+ T cells with low clonality is induced by chemotaxis in the HIGH group, possibly leading to poor prognosis of GC patients.
Project description:Lung cancer is the leading cause of death from malignant diseases worldwide, with the non-small cell (NSCLC) subtype accounting for the majority of cases. NSCLC is characterized by frequent genomic imbalances and copy number variations (CNVs), but the epigenetic aberrations that are associated with clinical prognosis and therapeutic failure remain not completely identify. In the present study, a total of 55 lung cancer patients were included and we conducted genomic and genetic expression analyses, immunohistochemical protein detection, DNA methylation and chromatin immunoprecipitation assays to obtain genetic and epigenetic profiles associated to prognosis and chemoresponse of NSCLC patients. Finally, siRNA transfection-mediated genetic silencing and cisplatinum cellular cytotoxicity assays in NSCLC cell lines A-427 and INER-37 were assesed to described chemoresistance mechanisms involved. Our results identified high frequencies of CNVs (60% of cases) in the 7p22.3-p21.1 and 7p15.3-p15.2 cytogenetic regions. However, overexpression of genes, such as MEOX2, HDAC9, TWIST1 and AhR, at 7p21.2-p21.1 locus occurred despite the absence of CNVs and little changes in DNA methylation. In contrast, the promoter sequences of MEOX2 and TWIST1 displayed significantly lower/decrease in the repressive histone mark H3K27me3 and increased in the active histone mark H3K4me3 levels. Finally these results correlate with poor survival in NSCLC patients and cellular chemoresistance to oncologic drugs in NSCLC cell lines in a MEOX2 and TWIST1 overexpression dependent-manner. In conclusion, we report for the first time that MEOX2 participates in chemoresistance irrespective of high CNV, but it is significantly dependent upon H3K27me3 enrichment probably associated with aggressiveness and chemotherapy failure in NSCLC patients, however additional clinical studies must be performed to confirm our findings as new probable clinical markers in NSCLC patients. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from fresh frozen, and paraffin embedded lung tumor samples Copy number analysis of Affymetrix 500K SNP arrays was performed for 33 lung tumor samples, including lung precursor metaplasia, lung tumors and cell lines. Six samples were also hybridized on the Affymetrix SNP 6.0 array