L-OHP resistant gastric cancer organoid
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ABSTRACT:
PROVIDER: PRJNA1180444 | ENA |
REPOSITORIES: ENA
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Project description:The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases.
2024-12-25 | GSE280740 | GEO
Project description:The discrepancy between organoid and immortalized cell line cultures for cancer target discovery remains unclear. Here, our multi-tiered CRISPR screens reveal in vivo-relevant metabolic dependencies and synthetic lethal pairs that can be uncovered with tumor organoids but not cell lines or even 3D spheroids. These screens identify lanosterol synthase and acetyl-CoA carboxylase inhibitors as effective treatments that impede xenografted tumor growth in mice. These lipid metabolic inhibitors exhibit nanomolar IC50 values across diverse human gastric cancer organoids resistant to first-line treatments. Mechanistically, gastric cancer organoids and in vivo tumor exhibit lipid metabolic adaptations not seen in 2D in vitro cultures. Additionally, enteric neurons modulate lipid metabolism in tumor organoids, altering drug sensitivity by up to two orders of magnitude. A neuron-cocultured CRISPR screen further reveals that acetyl-CoA carboxylase expression determines lanosterol synthase inhibitor efficacy. These findings highlight the critical roles of organoid environment and neuronal interaction in cancer lipid reliance.
2025-09-02 | GSE303453 | GEO
Project description:A combined enteric neuron-gastric tumor organoid reveals metabolic vulnerabilities in gastric cancer
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Project description:Copy number profiling of MKN45T 5-FU resistant gastric cancer cell lines and its parental cell line MKN45. We hypothesized that a detailed fine-scale survey of genomic CNAs might reveal the mechanism for acquired resistant to 5-FU in gastric cancer.
2017-06-09 | GSE89191 | GEO
Project description:One of the first-line chemotherapy regimes for gastric cancer is a combination treatment of epirubicin, cisplatin, and 5-fluorouracil (ECF). Chemoresistance remains the major obstacle to achieving successful results from gastric cancer treatment. Understanding acquired or pre-existing resistance to anticancer drugs is essential to the development of a therapeutic modality for gastric cancer. In this study, we established ECF-resistant (ECF-R) gastric cancer cell lines. We found that nerve injury–induced protein 2 (Ninjurin2, NINJ2) functioned as a biomarker for ECF-R in both gastric cancer cells. We also investigated the NINJ2 binding molecule and downstream pathway using both LC-MS/MS and phospho-antibody arrays.
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Project description:Gastric organoid single-cell RNA-seq
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Project description:We explored the potential of human gastric organoids as models for mucus production. Immunofluorescence staining confirmed that the organoids produced mucus containing MUC5AC and MUC6. The luminal mucus had viscoelastic properties similar to those of native human gastric mucus, as determined by particle tracking microrheology. To collect organoid-produced gastric mucus, termed bioengineered gastric mucus (BGM), organoids were cultured as monolayers at the air-liquid interface (ALI), and apically-secreted mucus was harvested and analyzed by MUC5AC ELISA, proteomics, CryoFE-SEM, and bulk rheometry. BGM contained high-molecular weight molecules also found in native gastric mucus, including MUC5AC. Proteomic analysis confirmed that BGM contained MUC5AC, MUC6, MUC1, and other stomach-specific molecules such as gastricsin, olfactomedin 4, and gastrokine. CryoFE-SEM showed that both BGM and native mucus had a porous structure and a characteristic honeycomb scaffold. Bulk rheometry confirmed that BGM exhibited shear thinning and predominantly elastic behavior, consistent with native mucus. Collectively, these findings indicate that BGM is an accessible alternative to native gastric mucus that can be produced on-demand for in vitro studies.
2025-12-30 | PXD072060 | Pride
Project description:To understand the molecular basis of the acquisition of 5-FU resistance in gastric cancer stem cells, we established 5-FU-resistant gastric cancer organoids. We used microarrays to detail the global program of gene expression underlying 5-FU resistance and maintenance of stem cell properties in gastric cancer.
2020-07-10 | GSE154127 | GEO
Project description:Gastric organoid single-cell RNA-seq II
| PRJNA499102 | ENA