Project description:To identify altered transcriptomic profiles in early-onset diffuse gastric cancer (DGC), we performed RNA sequencing on DGCs collected from 80 young (≤ 45 years) Korean patients who had not been treated with chemotherapy or radiation
Project description:Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7,804 or 5,166 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 132 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.
Project description:We report a comprehensive proteomic analysis of diffuse-type gastric cancer (DGC) (n=83), intestinal-type gastric cancer (IGC) (n=102), mixed-type gastric cancer (MGC) (n=11), and paired normal adjacent tissues (NATs), including data obtained by proteomics, phospho-proteomics profiling and TFs activity profiling.
Project description:To identify the specific genes for intestinal-type and diffuse-type gastric cancers. We selected 18 intestinal-type gastric cancers and 12 diffuse-type gastric cancers showing typical characteristics on the form of cell growth (clustered or scattered) and the degree of differentiation (well/moderate or poor), and performed microarray analysis for obtaining genome-wide mRNA expression profiles.
Project description:Although recent advances in high-throughput technology have provided many insights into gastric cancer (GC), few reliable biomarkers for handling diffuse type GC are identified. Here, we aim to identify a signature classifying high risk diffuse type GC. To identify molecular subtypes of diffuse type GC, we generated RNA-seq based transcriptome data, which were generated using normal mucosa and tumor cells from 140 fresh frozen tissues including diffuse type GCs (n = 107). Unsupervised hierarchical cluster analysis of the RNA-seq data revealed three distinct subgroups of GC. Based on these subtypes, we generated a signature reflecting the best characteristics of aggressive diffuse type GC. When estimating prognostic value, the signature showed a strong prediction ability and an independent clinical utility in diffuse type GC patients. Our signature represents a promising diagnostic tool for the identification of diffuse type GC patients that have a high risk of poor clinical behavior.
Project description:Specificity protein 1 (SP1) is an essential transcription factor regulating multiple cancer-related genes. Since aberrant expression of SP1 was known to be related to cancer development and progression, we focused on SP1 expression in gastric carcinoma and its correlation with disease outcomes. We discovered a different relationship between SP1 expression and patient survival in intestinal- and diffuse-type gastric cancer. In diffuse-type gastric cancer, patient survival decreased as SP1 expression increased (P < 0.05) in accordance with previously published papers, whereas the lack of SP1 expression in intestinal-type gastric cancer was correlated significantly with poor survival (P < 0.05). When SP1 downregulation was forced in high SP1 expressor intestinal-type gastric cell line MKN28 with siRNA, both migration and invasion were increased but cell proliferation was decreased. In accordance with these results, microarray data in siRNA-transfected MKN28 showed that genes inhibiting migration were downregulated and the expression of genes negatively facilitating proliferation was increased. Both migration and invasion, however, in low SP1 expressor intestinal-type gastric cell line AGS were decreased by forced SP1 expression. In contrast to intestinal-type, in diffuse-type gastric cell line SNU484, high SP1 expressor, both migration and invasion were decreased by siRNA. Contrary to previous studies, which did not reflect differences between the 2 histological types, our results showed that low expression of SP1 is involved in cancer progression and metastasis, and has a different effect on intestinal-type compared to diffuse-type gastric adenocarcinoma. 2 samples for MKN28 cells: si-SP1 against si-control and dyeswap of it upon 72 hour
Project description:Peritoneal carcinomatosis is a frequent finding in patients with primary gastric cancer, and it is associated with a poor prognosis. A major mechanism in peritoneal carcinomatosis is the dissemination of cancer cells into the abdominal cavity, mainly in diffuse gastric adenocarcinoma. The features that enable diffuse primary gastric tumours to develop peritoneal dissemination have been little investigated and are only incompletely understood. We therefore compared the gene expression profile in patients with diffuse primary gastric cancer with and without peritoneal carcinomatosis. Specimens from consecutive gastric cancer patients with and without peritoneal carcinomatosis were investigated using oligonucleotide microarrays. Keywords: Disease state analysis
Project description:To identify a cancer-associated fibroblast (CAF)-specific molecule that contributes to tumor-promoting effect, we utilized trnascriptome analysis. We performed RNA-sequencing with three normal fibroblast (NF)-CAF pairs derived from diffuse-type gastric cancer patients’ tissues. RNA-sequencing revealed several commonly increased CAF-specific genes among each pair.