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Updated: Jul 9, 2025
Non-invasive Assessment of the Efficacy of New Therapeutics for Intestinal Pathologies Using Serial Endoscopic Imaging of Live Mice
Published on: March 10, 2015
Comprehensive analysis reveals key genes and environmental toxin exposures underlying treatment response in
Yizhou Huang1, Jie Liu2, Dingbao Liang1
1Department of Gastroenterology, The PLA Navy Anqing Hospital, Anqing 246000, Anhui Province, China.
Background:
UC is increasingly prevalent worldwide and represents a significant global disease burden. Although medical therapeutics are employed, they often fall short of being optimal, leaving patients struggling with treatment non-responsiveness and many related complications.
Materials And Methods:
The study utilized gene microarray data and clinical information from GEO. Gene enrichment and differential expression analyses were conducted using Metascape and Limma, respectively. Lasso Regression Algorithm was constructed using glmnet and heat maps were generated using pheatmap. ROC curves were used to assess diagnostic parameter capability, while XSum was employed to screen for small-molecule drugs exacerbating UC. Molecular docking was carried out using Autodock Vina. The study also performed Mendelian randomization analysis based on TwoSampleMR and used CTD to investigate the relationship between exposure to environmental chemical toxicants and UC therapy responsiveness.
Results:
Six genes (ELL2, DAPP1, SAMD9L, CD38, IGSF6, and LYN) were found to be significantly overexpressed in UC patient samples that did not respond to multiple therapies. Lasso analysis identified ELL2 and DAPP1 as key genes influencing UC treatment response. Both genes accurately predicted intestinal inflammation in UC and impacted the immunological infiltration status. Clofibrate showed therapeutic potential for UC by binding to ELL2 and DAPP1 proteins. The study also reviews environmental toxins and drug exposures that could impact UC progression.
Conclusions:
We used microarray technology to identify DAPP1 and ELL2 as key genes that impact UC treatment response and inflammatory progression. Clofibrate was identified as a promising UC treatment. Our review also highlights the impact of environmental toxins on UC treatment response, providing valuable insights for personalized clinical management.
Insights
This study identifies DAPP1 and ELL2 as key genes influencing ulcerative colitis (UC) treatment response. Clofibrate shows promise as a novel therapeutic for UC, with environmental factors also impacting disease progression.
Area of Science:
- Genomics
- Immunology
- Pharmacology
Background:
- Ulcerative colitis (UC) presents a growing global health challenge with suboptimal treatment outcomes.
- Existing therapies for UC often result in treatment non-responsiveness and complications.
Approach:
- Gene microarray data and clinical information were analyzed using bioinformatics tools (Metascape, Limma, glmnet).
- Molecular docking and Mendelian randomization analyses investigated drug-gene interactions and environmental toxicant impacts.
- Diagnostic capability was assessed using ROC curves, and small-molecule drugs were screened for UC exacerbation.
Key Points:
- Six genes, including ELL2 and DAPP1, were significantly overexpressed in therapy-resistant UC.
- ELL2 and DAPP1 were identified as critical predictors of UC treatment response and inflammation.
- Clofibrate demonstrated therapeutic potential by binding to ELL2 and DAPP1.
Conclusions:
- DAPP1 and ELL2 are key genetic markers for UC treatment response and inflammatory progression.
- Clofibrate emerges as a potential novel therapeutic agent for ulcerative colitis.
- Environmental toxins and drug exposures significantly influence UC progression and treatment efficacy.
