Project description:We performed high throughput transcriptome of breast cancer and normal tissues, identifying lincRNA associated molecular subtype with powerful capacity to distinct breast cancer population and predict prognosis. We also identified subtype-specific lincRNAs that may be a useful complement to intrinsic molecular subtype classification when divergence emerges among pathologists.Paired-end transcriptome sequencing were carried out on a cohort of 33 breast tissues from 11 groups including five breast cancer subtypes including luminal A (LA), luminal B (HER2 negative)(LB, HER2-), luminal B (HER2 positive) (LB, HER2+), HER2 and tripple negative breast cancer (TNB), adjacent noncancerous breast tissue (ANT, three samples for each subtype) and the complete normal breast tissues (three samples)
Project description:Both present hemagglutinins and anti HLA antibodies bind to vascular endothelial cells in kidney transplantation, however in some patients this antibody-endothelial interaction is not associated with obvious tissue injury. Mechanisms of this phenomenon called accommodation remain poorly understood. Illumina Human HT-12 v4 Expression BeadChips whole renal transcriptome was evaluated in 3-months protocol biopsies with isolated C4d staining in otherwise stable ABO incompatible and HLA incompatible DSA positive kidney grafts (n=18) as well as in C4d negative HLA compatible grafts with normal histological findings (n=8). Top differently regulated genes were further validated using RT-qPCR at the independent patient cohort (n=24). GO terms with the highest fold enrichment revealed by gene annotation analysis of deregulated genes between ABOi and HLAi groups were represented by cadmium ion binding (p<0.01), apical plasma membrane (p<0.01) and anion transmembrane transporter activity (p<0.05). Majority of deregulated genes between both groups belongs to metallothioneins (MT) and solute carrier family (Slc) genes. The decreased expression of 5 Slc family genes (SLC4A1; SLC4A9; SLC17A3; SLC12A3; SLC30A2) and 3 metallothioneins of class1 (MT1F, MT1G and MT1X) in ABOi compared to HLAi group was verified by RT-qPCR. The most deregulated genes in C4d negative compared with C4d positive cohorts were those included in GO term “mitochondrion” which suggests the activation of metabolism in complement activation. In conclusion, hemagglutinin- and anti-HLA antibody-endothelial interactions and complement activation lead to different regulation of metallothioneins and distinct solute carrier family genes, which suggests its specific role in the accommodation phenomenon.
Project description:The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset. We analyzed RNA-seq data from a survey panel consisting of 8 benign breast lesions, 8 ER+, 8 triple negative, and 8 HER2-positive primary breast tumors to identify genomic features that were uniquely associated with HER2-positive tumors
Project description:We separately analyzed the HER2-negative and HER2-positive components of 12 HER2 heterogeneous breast cancers using gene copy number profiling and massively parallel sequencing, and identified potential driver genetic alterations restricted to the HER2-negative cells in each case. Our results indicate that even driver genetic alterations, such as HER2, can be heterogeneously distributed in a cancer, and that the HER2-negative components are likely driven by genetic alterations not present in the HER2-positive components, including BRF2 and DSN1 amplification.
Project description:The goal of our study is to build an integrated transcriptome landscape model for HER2 positive breast tumors and identify the crucial signaling pathways associated with HER2 tumors. Genomic features include, 685 genes that were differentially expressed only in HER2-positive tumors, 102 genes that were alternatively spliced in a pattern that is unique to HER2-positive tumors, and 303 genes that expressed single nucleotide sequence variants (eSNVs) that were unique to HER2-positive tumors. Network analysis was performed to integrate the genomic features into a transcriptome landscape model that identified 12 highly interconnected cellular processes that appear to be critical to the establishment and maintenance of HER2-positive tumors. We observed that integrin signaling was linked to lapatinib sensitivity in vitro and strongly associated with risk of relapse in the NCCTG N9831 adjuvant trastuzumab clinical trial dataset.