THER: Integrative Web Tool for Tumor Hypoxia Exploration and Research DOI

Yasi Zhang,

Anqi Lin, Hong Yang

et al.

Published: Jan. 1, 2023

­­­­­­Background: Hypoxia is an important factor in the adaptation of tumor cells to their environment, contributes malignant progression, and affects prognosis drug sensitivity. Although there a wealth transcriptomic data stored public databases, lack web-based tools for analyzing these explore link between hypoxia mechanisms tumorigenesis progression. Methods: We have developed interactive tool called THER, which designed help users easily identify potential targets, action effective drugs treating hypoxic tumors. THER integrates 63 datasets from Gene Expression Omnibus (GEO) database, covering 3 species, 18 types 42 cell line types. Findings: This web provides five modules that allow perform differential expression analysis, profiling correlation enrichment analysis sensitivity on different based oxygen statuses. Users can use autonomously various features samples under hypoxia/normoxia conditions investigate changes occur tumors environments.Interpretation: expect will be able valuable biomarkers, further reveal molecular hypoxia, drugs, thus providing scientific basis diagnosis treatment. open all accessed without login at https://smuonco.shinyapps.io/THER/.Funding: None.Declaration Interest: The authors declare no conflict interest.

Language: Английский

Overexpression of SLC2A1, ALDOC, and PFKFB4 in the glycolysis pathway drives strong drug resistance in 3D HeLa tumor cell spheroids DOI
Tong Wang, Xueting Wang,

Xuli Zheng

et al.

Biotechnology Journal, Journal Year: 2024, Volume and Issue: 19(9)

Published: Sept. 1, 2024

Abstract The 3D multicellular tumor spheroid (MTS) model exhibits enhanced fidelity in replicating the microenvironment and demonstrates exceptional resistance to clinical drugs compared 2D monolayer model. In this study, we used multiomics (transcriptome, proteomics, metabolomics) tools explore molecular mechanisms metabolic differences of two culture models. Analysis Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) enrichment pathways revealed that differentially expressed genes between models were mainly enriched cellular components biological processes associated with extracellular matrix, structural organization, mitochondrial function. An integrated analysis three omics data 11 possible drug targets. Among these targets, seven genes, AKR1B1 , ALDOC GFPT2 GYS1 LAMB2 PFKFB4 SLC2A1 exhibited significant upregulation. Conversely, four COA7 DLD IFNGR1 QRSL1 significantly downregulated. Clinical prognostic using TCGA survival database indicated high‐expression groups a negative correlation patient survival. We further validated their involvement chemotherapy resistance, indicating potential significance improving prognosis outcomes. These results provide valuable insights into therapeutic targets can potentially enhance treatment efficacy

Language: Английский

Citations

0
Fructose-bisphosphate Aldolase C Expression is Associated with Poor Prognosis and Stemness in Gastric Cancer DOI Open Access
Akira Ishikawa,

Yuki Shiwa,

Narutaka Katsuya

et al.

ACTA HISTOCHEMICA ET CYTOCHEMICA, Journal Year: 2024, Volume and Issue: 57(5), P. 165 - 174

Published: Oct. 22, 2024

Gastric cancer (GC) is the third leading cause of cancer-related deaths in Japan, underscoring urgent need for deeper insights into its pathogenesis. Spheroids provide a more realistic and versatile model studying cancers stem cells (CSCs). While fructose-bisphosphate aldolase C (ALDOC) has been identified colorectal spheroids, role GC remained largely unexplored. This study aimed to elucidate ALDOC by performing single-cell functional analyses spheroids cell lines, along with immunohistochemistry 127 samples assess correlation CSC markers. Our analysis revealed upregulation pseudotime indicating that ALDOC-expressing were predominantly undifferentiated co-expressed LGR5 CD44. Further investigation cell-cell interactions suggested state may be maintained WNT, BMP, EGF signaling. Functional assays demonstrated knockdown led marked reduction growth, invasiveness, spheroid colony formation capacity lines. Clinically, was detected cytoplasm 56.7% (72/127) cases, high expression significantly associated poor overall survival (

Language: Английский

Citations

0
THER: Integrative Web Tool for Tumor Hypoxia Exploration and Research DOI Creative Commons

Yasi Zhang,

Anqi Lin, Hong Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 22, 2023

Abstract Hypoxia is an important factor in the adaptation of tumor cells to their environment, contributes malignant progression, and affects prognosis drug sensitivity. Although there a wealth transcriptomic data stored public databases, lack web-based tools for analyzing these explore link between hypoxia mechanisms tumorigenesis progression. To this end, we have developed interactive tool called THER, which designed help users easily identify potential targets, action effective drugs treating hypoxic tumors. THER integrates 63 datasets from Gene Expression Omnibus (GEO) database, covering 3 species, 18 types 42 cell line types. This web provides five modules that allow perform differential expression analysis, profiling correlation enrichment analysis sensitivity on different based oxygen statuses. We expect will be able use valuable biomarkers, further reveal molecular hypoxia, drugs, thus providing scientific basis diagnosis treatment. open all can accessed without login at https://smuonco.shinyapps.io/THER/ .

Language: Английский

Citations

0
Identification of a set of genes potentially responsible for resistance to ferroptosis in lung adenocarcinoma cancer stem cells DOI Creative Commons
Rita Mancini, Francesca Ascenzi, Antonella Esposito

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 20, 2023

Abstract Scientific literature supports the evidence that Cancer Stem Cells (CSCs) retain inside low Reactive Oxygen Species (ROS) levels and are therefore less susceptible to cell death, including ferroptosis, a type of death dependent on iron-driven lipid peroxidation. A collection lung adenocarcinoma (LUAD) primary lines derived from malignant pleural effusions (MPEs) patients was used obtain 3D spheroids enriched for stem-like properties. We observed ferroptosis inducer RSL3 triggered peroxidation in LUAD cells when grown 2D conditions; however, condition, all underwent phenotypic switch, exhibiting substantial resistance protection against ferroptotic death. Interestingly, this phenomenon reversed by disrupting growing them back adherence, supporting idea CSCs plasticity, which holds cancer have dynamic ability transition between CSC state non-CSC state. Molecular analyses showed correlated with an increased expression antioxidant genes high proteins involved iron storage export, indicating oxidative stress availability initiation ferroptosis. Moreover, transcriptomic highlighted novel subset commonly modulated potentially capable driving CSCs, thus allowing better understand mechanisms CSC-mediated drug tumors.

Language: Английский

Citations

0
THER: Integrative Web Tool for Tumor Hypoxia Exploration and Research DOI

Yasi Zhang,

Anqi Lin, Hong Yang

et al.

Published: Jan. 1, 2023

­­­­­­Background: Hypoxia is an important factor in the adaptation of tumor cells to their environment, contributes malignant progression, and affects prognosis drug sensitivity. Although there a wealth transcriptomic data stored public databases, lack web-based tools for analyzing these explore link between hypoxia mechanisms tumorigenesis progression. Methods: We have developed interactive tool called THER, which designed help users easily identify potential targets, action effective drugs treating hypoxic tumors. THER integrates 63 datasets from Gene Expression Omnibus (GEO) database, covering 3 species, 18 types 42 cell line types. Findings: This web provides five modules that allow perform differential expression analysis, profiling correlation enrichment analysis sensitivity on different based oxygen statuses. Users can use autonomously various features samples under hypoxia/normoxia conditions investigate changes occur tumors environments.Interpretation: expect will be able valuable biomarkers, further reveal molecular hypoxia, drugs, thus providing scientific basis diagnosis treatment. open all accessed without login at https://smuonco.shinyapps.io/THER/.Funding: None.Declaration Interest: The authors declare no conflict interest.

Language: Английский

Citations

0