ArticleClinical cancer research : an official journal of the American Association for Cancer Research2022
Transcriptomic Profiling of MSI-H/dMMR Gastrointestinal Tumors to Identify Determinants of Responsiveness to Anti-PD-1 Therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 62 citations in OpenAlex.
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- Preoperative liquid biopsy transcriptomic panel for risk assessment of lymph node metastasis in T1 gastric cancer.Journal of experimental & clinical cancer research : CR · 2025Article
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- Evolving Strategies in the Management of Microsatellite Instability-High/Mismatch Repair Deficient Esophagogastric Adenocarcinoma.Current oncology reports · 2025Review
- ANXA10 sensitizes microsatellite instability-high colorectal cancer to anti-PD-1 immunotherapy via assembly of HLA-DR dimers by regulating CD74.Cell biology and toxicology · 2025Article
- Identification of Molecular Subtypes and Prognostic Features of Breast Cancer Based on TGF-β Signaling-related Genes.Cancer informatics · 2025Article
- Applications and advances of multi-omics technologies in gastrointestinal tumors.Frontiers in medicine · 2025Review
- Cap-specific terminal N6-methyladeonsine methylation of RNA mediated by PCIF1 and possible therapeutic implications.Genes & diseases · 2025Review
- Advances in the diagnosis and treatment of MET-variant digestive tract tumors.World journal of gastrointestinal oncology · 2024Review
- SPP1+ macrophages and FAP+ fibroblasts promote the progression of pMMR gastric cancer.Scientific reports · 2024Article
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- Research advances in the molecular classification of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Review
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTranscriptomic profiling was performed for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) gastrointestinal tumors to determine the predictors of response to PD-1 blockade. EXPERIMENTAL
designThirty-six patients with MSI-H/dMMR gastrointestinal tumors, including gastric cancer, colorectal cancer, cholangiocarcinoma, small intestine cancer, and pancreatic cancer, being treated with PD-1 blockade were analyzed. We conducted the transcriptomic analysis of gastrointestinal tumors using RNA sequencing data, including the consensus molecular subtypes (CMS) of colorectal cancer.
resultsGene set enrichment analysis (GSEA) demonstrated that non-responders had upregulations of epithelial-mesenchymal transition, angiogenesis, hypoxia, mTORC1, TNF-α, KRAS, Wnt/β-catenin, TGF-β, and various metabolism-related signaling pathways. Meanwhile, the IFNγ pathway was enriched in responders. On the basis of the leading-edge analysis of GSEA, VEGF-A was significantly correlated with enriched pathways in non-responders. Patients with high VEGF-A expression, compared with those with low expression, had significantly shorter progression-free survival [PFS; median 4.8 months vs. not reached (NR), P = 0.032] and overall survival (median 11.1 months vs. NR, P = 0.045). Among 13 patients with colorectal cancer evaluable for CMS classification, the objective response rate was 100%, 0%, 0%, and 16.7% in CMS1, CMS2, CMS3, and CMS4, respectively. Patients with CMS1 had significantly longer PFS (NR vs. 4.8 months, P = 0.017) than those with CMS2, CMS3, or CMS4.
conclusionsSeveral transcriptomic features, including CMS classification and related genes, were associated with response to PD-1 blockade in MSI-H/dMMR gastrointestinal tumors. These findings can help develop predictive biomarkers or combination immunotherapies.
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