Project description:To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility We performed an exome chip-based array study in 329 gastric cancer cases and 683 controls.
Project description:To efficiently identify genetic susceptibility variants for gastric cancer, including rare coding variants, we performed an exome chip-based array study. We found that a linkage disequilibrium (LD) block containing 2 significant variants in PSCA gene increased the risk and two blocks that included 15 suggested variants including TRIM31, TRIM 40, TRIM 10, and TRIM26 regions, and included one suggested variant and OR2H2 gene showed protective associations with gastric cancer susceptibility. In addition, the PLEC region (rs200893203), FBLN2 region (rs201192415), and EPHA2 region (rs3754334) were associated with increased susceptibility
Project description:Deregulated gene expression is a hallmark of cancer, however most studies to date have analyzed short-read RNA-sequencing data with inherent limitations. Here, we combine PacBio long-read isoform sequencing (Iso-Seq) and Illumina paired-end short read RNA sequencing to comprehensively survey the transcriptome of gastric cancer (GC), a leading cause of global cancer mortality. We performed full-length transcriptome analysis across 10 GC cell lines covering four major GC molecular subtypes (chromosomal unstable, Epstein-Barr positive, genome stable and microsatellite unstable). We identify 60,239 non-redundant full-length transcripts, of which >66% are novel compared to current transcriptome databases. Novel isoforms are more likely to be cell-line and subtype specific, expressed at lower levels with larger number of exons, with longer isoform/coding sequence lengths. Most novel isoforms utilize an alternate first exon, and compared to other alternative splicing categories are expressed at higher levels and exhibit higher variability. Collectively, we observe alternate promoter usage in 25% of detected genes, with the majority (84.2%) of known/novel promoter pairs exhibiting potential changes in their coding sequences. Mapping these alternate promoters to TCGA GC samples, we identify several cancer-associated isoforms, including novel variants of oncogenes. Tumor-specific transcript isoforms tend to alter protein coding sequences to a larger extent than other isoforms. Analysis of outcome data suggests that novel isoforms may impart additional prognostic information. Our results provide a rich resource of full-length transcriptome data for deeper studies of GC and other gastrointestinal malignancies.
Project description:As a subpopulation of tumor cells with stemness characteristics such as self-renewal ability and high oncogenicity, gastric cancer stem cells (GCSCs) are considered to be tumor-initiating cells and are the root cause of cancer recurrence and chemoresistance. Therefore, an in-depth study of the stemness characteristics and maintenance mechanism of GCSCs is of great significance for the treatment of gastric cancer (GC). In this study, GCSCs and non-gastric cancer stem cells (Non-GCSCs) derived from tumor tissues of GC patients were used for whole transcriptome sequencing. The goal of identifying key differentially expressed circRNAs, lncRNAs, miRNAs and mRNAs associated with GCSCs. In conclusion, we mapped the molecular feathers at RNA level closely related to GCSCs and revealed certain ncRNAs with great research potentia based on the whole transcriptome sequencing.
Project description:Gastric cancer is the fourth common cancer and second leading cause of cancer related mortality. The survival probability of gastric cancer patients is often less due to the diagnosis at late stage and also due to the heterogenous nature of tumors. Molecular and transcriptome-wide understanding of the dysregulations in gastric tumors from different populations is highly required to delineate the heterogeneity. To delineate the key oncogenic dysregulations in terms of the transcripts, transcription programs and signaling pathways, we performed genome-wide mRNA profiling of human gastric normal and gastric cancer tissues using Affymetrix Human Transcriptome 2.0 arrays.