Project description:<p>To identify candidate drivers involved in oncogenesis and tumor evolution, we conducted an extensive genome sequencing analysis of metastatic progression in diffuse gastric cancer. This involved a comparison between a primary tumor from a Hereditary Diffuse Gastric Cancer Syndrome proband and its subsequent recurrence as an ovarian metastasis.</p>
Project description:Gastric cancer (GC) remains one of the most prevalent tumor worldwide, and ranks third in cancer-related deaths globally. Long non-coding RNAs (lncRNAs) have been reported to play significant role in the progression and metastasis in gastric cancer (GC), however, the molecular mechanism are largely elusive. We aim to identify up-regulated lncRNA in gastric cancer peritoneal metastasis and study their function in promoting tumor progression and metastasis.
Project description:Human primary gastric cancer tissue SAGE libraries. Profile of the genes expressed in well and poorly differentiated gastric cancer, early and advanced gastric cancer, scirrhous type gastric cancer, and lymph node metastasis determined through SAGE. Keywords = gastric cancer, histology, early gastric cancer, advanced gastric cancer, lymph node metastasis, scirrhous type gastric cancer Keywords: other
Project description:Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition of RUNX3 in gastric cancer cell lines reduced migration, invasion, and anchorage independent growth in vitro. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression of xenograft growth and liver metastasis. We interrogated the potential of RUNX3 as a metastasis driver in gastric cancer by profiling its target genes. Transcriptomic analysis revealed strong involvement of RUNX3 in the regulation of multiple developmental pathways, consistent with the notion that RUNX family genes are master regulators of development. RUNX3 promoted “cell migration” and “extracellular matrix” programs, which are necessary for metastasis. Of note, we found pro-metastatic genes WNT5A, CD44 and VIM among the top differentially expressed genes in RUNX3-knockout versus control cells. Chromatin immunoprecipitation sequencing and HiChIP analyses revealed that RUNX3 bound to the enhancers and promoters of these genes, suggesting that they are under direct transcriptional control by RUNX3. We show that RUNX3 promoted metastasis in part through its upregulation of WNT5A to promote migration, invasion, and anchorage-independent growth in various malignancies. Our study therefore reveals the RUNX3-WNT5A axis as a key targetable mechanism for gastric cancer metastasis.
Project description:Metastasis is a major problem of gastric cancer. In this study, small extracellular vesicle (sEV)-derived miRNAs were sequenced to screen biomarkers for GC’s organo-tropic metastasis. Plasma from 40 treatment-naïve gastric cancer patients including 10 no metastasis (M0) and 30 distant metastasis (M1) were assessed by sEV-miRNA-sequencing. sEV miRNAs with diverse expression profiles across different metastatic patterns were combined into sigantures to characterize and predict gastric cancer metastasis.
Project description:Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition of RUNX3 in gastric cancer cell lines reduced migration, invasion, and anchorage independent growth in vitro. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression of xenograft growth and liver metastasis. We interrogated the potential of RUNX3 as a metastasis driver in gastric cancer by profiling its target genes. Transcriptomic analysis revealed strong involvement of RUNX3 in the regulation of multiple developmental pathways, consistent with the notion that RUNX family genes are master regulators of development. RUNX3 promoted “cell migration” and “extracellular matrix” programs, which are necessary for metastasis. Of note, we found pro-metastatic genes WNT5A, CD44 and VIM among the top differentially expressed genes in RUNX3-knockout versus control cells. Chromatin immunoprecipitation sequencing and HiChIP analyses revealed that RUNX3 bound to the enhancers and promoters of these genes, suggesting that they are under direct transcriptional control by RUNX3. We show that RUNX3 promoted metastasis in part through its upregulation of WNT5A to promote migration, invasion, and anchorage-independent growth in various malignancies. Our study therefore reveals the RUNX3-WNT5A axis as a key targetable mechanism for gastric cancer metastasis.
Project description:Gastric cancer metastasis is a major cause of mortality worldwide. Inhibition of RUNX3 in gastric cancer cell lines reduced migration, invasion, and anchorage independent growth in vitro. Following splenic inoculation, CRISPR-mediated RUNX3-knockout HGC-27 cells show suppression of xenograft growth and liver metastasis. We interrogated the potential of RUNX3 as a metastasis driver in gastric cancer by profiling its target genes. Transcriptomic analysis revealed strong involvement of RUNX3 in the regulation of multiple developmental pathways, consistent with the notion that RUNX family genes are master regulators of development. RUNX3 promoted “cell migration” and “extracellular matrix” programs, which are necessary for metastasis. Of note, we found pro-metastatic genes WNT5A, CD44 and VIM among the top differentially expressed genes in RUNX3-knockout versus control cells. Chromatin immunoprecipitation sequencing and HiChIP analyses revealed that RUNX3 bound to the enhancers and promoters of these genes, suggesting that they are under direct transcriptional control by RUNX3. We show that RUNX3 promoted metastasis in part through its upregulation of WNT5A to promote migration, invasion, and anchorage-independent growth in various malignancies. Our study therefore reveals the RUNX3-WNT5A axis as a key targetable mechanism for gastric cancer metastasis.
Project description:Gastric cancer (GC) is a leading cause of cancer-induced mortality with poor prognosis with metastasis. However, the mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches mask roles of subpopulations. To answer questions from the gastric carcinoma intratumoral perspective in the metastasis, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using scRNA-seq. Results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared by a different patient. Clustering data showed significant intratumoral heterogeneity. Results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study we obtained a more comprehensive picture over gastric cancer lymph node metastasis, and we discovered some GC lymph node metastasis marker genes (ERBB2, CLDN11 and CDK12), as well as potential gastric cancer evolutionary driving genes (FOS and JUN), which provide a basis for the treatment of heterogeneity.
Project description: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.