ArticleMolecular cancer2004
Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity.
Article in Molecular cancer, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The Prognostic Implications of Tumor Infiltrating Lymphocytes in Colorectal Cancer: A Systematic Review and Meta-Analysis.Scientific reports · 2020Pooled it
- Trial
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- The Preoperative C-reactive Protein/Albumin Ratio of Immune-inflammation Index Is an Independent Prognostic Factor of Advanced Colorectal Cancer in Older Patients (≥ 65 years).Journal of the anus, rectum and colon · 2025Article
- GRP94 is an IGF-1R chaperone and regulates beta cell death in diabetes.Cell death & disease · 2024Article
- Genomic instability as a driver and suppressor of anti-tumor immunity.Frontiers in immunology · 2024Review
- Article
- Spontaneous Complete Regression of Colon Cancer Liver Metastases in a Lung Transplant Patient: A Case Report.Case reports in transplantation · 2023Article
- Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer.International journal of molecular sciences · 2022Review
- Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response.Nature communications · 2021Article
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
- Review
- Expression of Thomsen-Friedenreich Antigen in Colorectal Cancer and Association with Microsatellite Instability.International journal of molecular sciences · 2021Article
- The Therapeutic Potential of Tackling Tumor-Induced Dendritic Cell Dysfunction in Colorectal Cancer.Frontiers in immunology · 2021Review
- Identification of relevant genetic alterations in cancer using topological data analysis.Nature communications · 2020Article
- Friend or Foe: Prognostic and Immunotherapy Roles of BTLA in Colorectal Cancer.Frontiers in molecular biosciences · 2020Article
- Immune overdrive signature in colorectal tumor subset predicts poor clinical outcome.The Journal of clinical investigation · 2019Article
- Therapeutic implications of germline genetic findings in cancer.Nature reviews. Clinical oncology · 2019Review
- Immune checkpoint inhibitors in gastrointestinal malignancies.Journal of gastrointestinal oncology · 2018Review
- Immune Checkpoints as a Target for Colorectal Cancer Treatment.International journal of molecular sciences · 2017Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundColorectal cancers displaying high-degree microsatellite instability (MSI-H) have an improved prognosis compared to microsatellite stable (MSS) cancers. The observation of pronounced lymphocytic infiltrates suggests that MSI-H cancers are inherently more immunogenic. We aimed to compare the gene expression profiles of MSI-H and MSS cancers to provide evidence for an activated immune response in the former.
resultsWe analysed tissue from 133 colorectal cancer patients with full consent and Local Ethics Committee approval. Genomic DNA was analysed for microsatellite instability in BAT-26. High-quality RNA was used for microarray analysis on the Affymetrix HG-U133A chip. Data was analysed on GeneSpring software version 6.0. Confirmatory real-time RT-PCR was performed on 28 MSI-H and 26 MSS cancers. A comparison of 29 MSI-H and 104 MSS cancers identified 2070 genes that were differentially expressed between the two groups [P < 0.005]. Significantly, many key immunomodulatory genes were up-regulated in MSI-H cancers. These included antigen chaperone molecules (HSP-70, HSP-110, Calreticulin, gp96), pro-inflammatory cytokines (Interleukin (IL)-18, IL-15, IL-8, IL-24, IL-7) and cytotoxic mediators (Granulysin, Granzyme A). Quantitative RT-PCR confirmed up-regulation of HSP-70 [P = 0.016], HSP-110 [P = 0.002], IL-18 [P = 0.004], IL-8 [0.002] and Granulysin [P < 0.0001].
conclusionsThe upregulation of a large number of genes implicated in immune response supports the theory that MSI-H cancers are immunogenic. The novel observation of Heat Shock Protein up-regulation in MSI-H cancer is highly significant in light of the recognised roles of these proteins in innate and antigen-specific immunogenicity. Increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators also indicate an activated anti-tumour immune response.
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