Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy
Autor: | Pengwu Li, Ming-Qing Xu, Yong Gao, Xiaobo Zheng, Chune Yu, Jing Yu, Ming Zhang, Guiquan Fan |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Oncology
Cancer microenvironment Male medicine.medical_specialty Colorectal cancer Lymphocyte medicine.medical_treatment animal diseases Science chemical and pharmacologic phenomena medicine.disease_cause Subclass Article Cohort Studies Immune system Internal medicine medicine Biomarkers Tumor Humans Immunologic Factors Gene Mutation Multidisciplinary business.industry Cancer Immunotherapy biochemical phenomena metabolism and nutrition medicine.disease Prognosis Gene Expression Regulation Neoplastic medicine.anatomical_structure Tumour immunology bacteria Medicine Female Microsatellite Instability business Colorectal Neoplasms |
Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular classification system for colorectal cancer (CRC). We obtained data of 1503 CRC patients (training cohort: 488 from The Cancer Genome Atlas; validation cohort: 1015 from the Gene Expression Omnibus). In the training cohort, 42.8% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were subdivided into immune classes. Within the immune class, 53.1% of patients were associated with a worse overall prognosis and belonged to the immune-suppressed subclass, characterized by the activation of stroma-related signatures, genes, immune-suppressive cells, and signaling. The remaining immune class patients belonged to the immune-activated subclass, which was associated with a better prognosis and response to anti-PD-1 therapy. Immune-related subtypes were associated with different copy number alterations, tumor-infiltrating lymphocyte enrichment, PD-1/PD-L1 expression, mutation landscape, and cancer stemness. These results were validated in patients with microsatellite instable CRC. We described a novel immune-related class of CRC, which may be used for selecting candidate patients with CRC for immunotherapy and tailoring optimal immunotherapeutic treatment. |
Databáze: | OpenAIRE |
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