Genome-wide analysis of long noncoding RNA expression profile in gastric cancer peritoneal metastasis
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PROVIDER: PRJNA826104 | ENA |
REPOSITORIES: ENA
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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.
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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
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Project description:Peritoneal metastasis (PM) has a suppressive tumor immune microenvironment (TIME), which limits the effects of immunotherapy. This study aims to investigate the immunomodulatory effects of intraperitoneal administration of IL-33 on PM-associated TIME. Immunocompetent mice were used to investigate the role of IL-33 in development of abdominal dissemination and host outcome. Murine (m) and human (h) gastric cancer cells were tested for their response to IL-33 by qRT-PCR, flow cytometry, and immunofluorescence. Survival was significantly prolonged in patients with high Il-33 mRNA expression. Intraperitoneal administration of IL-33 could induce the celiac inflammatory environment, activate immunologic effector cells and reverse the immunosuppressive tumor microenvironment, which delayed tumor progression and peritoneal metastasis of gastric cancer. Mechanistically, IL-33 could induce M2 polarization by activating p38-GATA-binding protein 3 (GATA3) signaling pathway. IL-33 combined with anti-CSF1R or p38 inhibitor to regulate tumor-associated macrophages (TAMs) showed synergistic anti-tumor effect. Intraperitoneal administration of IL-33 inducing local inflammatory milieu provided a novel approach for the treatment of metastatic peritoneal malignancies, which combined with TAMs reprogramming to reshape TIME could achieve better treatment efficacy.
2023-06-30 | GSE235526 | GEO
Project description:RORγ hijacks HIF-1α to promote peritoneal metastasis of gastric cancer
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Project description:Gastric cancer (GC) constitutes a significant cause of cancer-related mortality worldwide, with metastatic patterns including hematogenous, peritoneal, and ovarian routes. Although GC gene expression patterns have been extensively researched, the metastasis-specific gene expression landscape remains largely unexplored. This study undertook a whole transcriptome sequencing analysis of 66 paired primary and metastatic (hematogenous, peritoneal, or ovarian) GC tumors from 14 patients, leading to the identification of 122 unique metastasis-specific epithelial-mesenchymal transition (msEMT) genes. These genes demonstrated varying expression patterns depending on the metastatic route, suggesting route-specific molecular mechanisms in GC metastasis. High expression of msEMT genes in primary tumors was associated with more frequent CDH1 mutations, the genomically stable subtype, and poor prognosis in The Cancer Genome Atlas GC cohort. This association was further corroborated by poor prognosis and high predictive performance for peritoneal or ovarian recurrence in two independent cohorts (GSE66229; n=300, GSE84437; n=433). Single-cell RNA sequencing analysis of primary tumors (GSE167297) and four independent ascites samples from GC patients revealed that msEMT genes were predominantly expressed in diverse fibroblast sub-populations, rather than cancer cells. This study illuminates the route-specific mechanisms and underlines the significance of msEMT genes and cancer-associated fibroblasts in GC metastasis, highlighting potential directions for future research.
2024-07-01 | GSE237876 | GEO
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 GC and study their function in promoting tumor progression and metastasis.
2023-11-13 | GSE193109 | GEO
Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis with peritoneal relapse free survival showed a significant difference between ‘good signature group’ and ‘poor signature group’ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers.
2009-03-04 | GSE15081 | GEO