Transcriptome sequencing of triple-matched samples of gastric cancer patients with ovarian metastasis
Ontology highlight
ABSTRACT: Our aim was to decipher the underlying molecular mechanism of synchronous ovarian metastasis of gastric cancer. We hereby conducted transcriptome sequencing of triple-matched samples including normal gastric mucosa, primary gastric cancer and ovarian metastatic tumors from 3 individual patients with the application of Illumina sequencing platform with 150-bp paired-end. Follow-up analyses not only identified differentially expressed genes between different sample sets (a threshold of fold change >2 and adjusted P value <0.05) but also uncovered significantly enriched signaling pathways of individual type. To sum up, our comparative transcriptomic analyses of triple-matched fresh samples stored in liquid nitrogen profiled the molecular expression and revealed functionally enriched pathways underlying the ovarian metastasis of gastric cancer.
Project description:Using LC-MS/MS, we analyzed ECM-enriched samples obtained from 1) human triple-negative breast cancer samples and matched adjacent normal mammary gland tissues, and 2) disease-free omentum from patient with non-metastatic ovarian cancer and high-grade- serous-ovarian- cancer-derived omental metastasis samples. We conducted the LC-MS/MS analysis on peptides obtained after solubilizing ECM-enriched samples using different methods (crude ECM extract, urea-soluble extract, urea-insoluble extract) and submitted to basic-reversed- phase separation or not.
Project description:To understand the molecular mechanism underlying ovarian metastasis of gastric cancer, we performed RNA-seq of paired primary tumor, normal mucosa and ovarian metastasis of four GC patients by the Illumina sequencing platform with 150-bp paired-end, followed by functional enrichment analyses of differentially expressed genes between three sample sets. A total number of 15,493 protein-coding genes were detected, the majority of which were the annotated human reference genes. Using a threshold of fold change >2 and adjusted P value <0.05, a total number of 3023 differentially expressed genes were detected between different sets of samples. Among them, 479 and 609 protein-coding genes were up- and down-regulated in ovarian metastases over primary tumors, respectively. Functional enrichment analyses revealed the significant enrichment of immune system, tumor microenvironment, metabolism and sex hormone-related pathways in the ovarian metastasis of gastric cancer. In conclusion, comparative transcriptome characterization of paired primary and ovarian metastatic tumor profiled the genome-wide molecular expression and unveiled functionally enriched pathways underlying this specific type of distant metastasis in GC.
Project description:Gastric cancer is one of the most aggressive cancers and is the second leading cause of cancer death worldwide. Approximately 40% of global gastric cancer cases occur in China, with peritoneal metastasis being the prevalent form of recurrence and metastasis in advanced disease (>50%). Currently, there are limited clinical approaches for predicting and treatment of peritoneal metastasis, resulting in a 6- month average survival time. By comprehensive genome analysis will uncover the pathogenesis of peritoneal metastasis. Here we describe a comprehensive whole-genome and transcriptome sequencing analysis of one advanced gastric cancer case, including non-cancerous mucosa, primary cancer and matched peritoneal metastatic cancer. The peripheral blood is used as normal control.
Project description:<p>In this study, linked read sequencing was performed on two ovarian metastases and matched normal tissue, from a patient with primary diffuse gastric cancer. Linked read sequencing is a DNA preparation technology whereby high molecular weight molecules of DNA are uniquely barcoded prior to fragmentation and sequencing, thus retaining information about genomic contiguity. This study performed an extended analysis of linked read sequencing data to resolve the complex structures of structural variants in the cancer genomes. Complex structural rearrangements were identified in the genomic region surrounding the known oncogene FGFR2, and the association between FGFR2 and gastric cancer metastasis was demonstrated in an organoid model. </p>
Project description:This SuperSeries is composed of the following subset Series: GSE33335: Expression data from gastric tissues: Cancer Samples vs. Matched Adjacent Noncancerous Samples GSE33428: Copy number variation profiling of gastric tissues: Cancer Samples vs. Matched Adjacent Noncancerous Samples Refer to individual Series
Project description:Although the main cause of gastrointestinal stromal tumor (GIST) is due to gain-of-function mutation of the c-kit gene in the interstitial cells of Cajal, concomitant genetic or epigenetic changes other than c-kit are thought to occur in the development of metastasis. We used microarrays to identify genes that were up-regulated and down-regulated in the metastatic liver GIST. Three primary gastric GISTs without synchronous or metachronous metastasis and five metastatic liver tumors originated from gastric GIST were utilized for RNA extraction and hybridization on Affymetrix microarrays. No patients had received imatinib therapy before surgery.