ArticleEBioMedicine2021
Crohn's disease-associated ATG16L1 T300A genotype is associated with improved survival in gastric cancer.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Canonical pathways and selective mechanisms of autophagy in inflammatory bowel disease.Advanced biotechnology · 2026Review
- Breaking barriers in prostate cancer: the mRNA vaccine breakthrough and what comes next.NPJ vaccines · 2026Review
- Molecular dynamics of the host response to Streptococcus pneumoniae pneumonia in baboons.Animal models and experimental medicine · 2025Article
- Predictive factors for neoadjuvant combined immunotherapy in gastric adenocarcinoma: Focusing on the primitive enterocyte phenotype and PVR.British journal of cancer · 2025Article
- Mild Duodenal Mucosal Injury and Increased Type I Interferon Signaling Are Preludes to Celiac Disease.Laboratory investigation; a journal of technical methods and pathology · 2025Article
- Mechanism of cell death and its application in the repair of inflammatory bowel disease by mesenchymal stem cells.Frontiers in immunology · 2025Review
- Western diet reduces small intestinal intraepithelial lymphocytes via FXR-Interferon pathway.Mucosal immunology · 2024Article
- Modulating autophagy to treat diseases: A revisited review on in silico methods.Journal of advanced research · 2024Review
- The dual role of autophagy in suppressing and promoting hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
- Association between Gastric Cancer and 12 Autoimmune Diseases: A Mendelian Randomization Study.Genes · 2023Article
- Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer.Nature communications · 2023Article
- Peroxisome proliferator-activated receptors regulate the progression and treatment of gastrointestinal cancers.Frontiers in pharmacology · 2023Review
- Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases.Autophagy · 2022Article
- Expression of Oxidative Phosphorylation Complexes and Mitochondrial Mass in Pediatric and Adult Inflammatory Bowel Disease.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundA non-synonymous single nucleotide polymorphism of the ATG16L1 gene, T300A, is a major Crohn's disease (CD) susceptibility allele, and is known to be associated with increased apoptosis induction in the small intestinal crypt base in CD subjects and mouse models. We hypothesized that ATG16L1 T300A genotype also correlates with increased tumor apoptosis and therefore could lead to superior clinical outcome in cancer subjects.
methodsT300A genotyping by Taqman assay was performed for gastric carcinoma subjects who underwent resection from two academic medical centers. Transcriptomic analysis was performed by RNA-seq on formalin-fixed paraffin-embedded cancerous tissue. Tumor apoptosis and autophagy were determined by cleaved caspase-3 and p62 immunohistochemistry, respectively. The subjects' genotypes were correlated with demographics, various histopathologic features, transcriptome, and clinical outcome.
findingsOf the 220 genotyped subjects, 163 (74%) subjects carried the T300A allele(s), including 55 (25%) homozygous and 108 (49%) heterozygous subjects. The T300A/T300A subjects had superior overall survival than the other groups. Their tumors were associated with increased CD-like lymphoid aggregates and increased tumor apoptosis without concurrent increase in tumor mitosis or defective autophagy. Transcriptomic analysis showed upregulation of WNT/β-catenin signaling and downregulation of PPAR, EGFR, and inflammatory chemokine pathways in tumors of T300A/T300A subjects.
interpretationGastric carcinoma of subjects with the T300A/T300A genotype is associated with repressed EGFR and PPAR pathways, increased tumor apoptosis, and improved overall survival. Genotyping gastric cancer subjects may provide additional insight for clinical stratification.
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