Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients

• Published in: Journal of translational medicine Vol. 19; no. 1; pp. 27 - 17
• Main Authors: Liu, Jungang, Huang, Xiaoliang, Liu, Haizhou, Wei, Chunyin, Ru, Haiming, Qin, Haiquan, Lai, Hao, Meng, Yongsheng, Wu, Guo, Xie, Weishun, Mo, Xianwei, Johnson, Caroline H., Zhang, Yawei, Tang, Weizhong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07.01.2021; BioMed Central; BMC
• Subjects: Antigens, Neoplasm; C-reactive protein; Cancer therapies; CD4 antigen; Chemotherapy; Colonic Neoplasms - genetics; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Datasets; Development and progression; DNA methylation; Gene expression; Genes, ras; Genetic aspects; Genomes; Growth factors; Health aspects; Hospitals; Human subjects; Humans; Immune system; Immunoglobulin M; Immunological memory; Immunology; Immunoregulation; Immunosuppression; Immunotherapy; Inflammation; K-Ras protein; Kinases; KRAS mutation; Lymphocytes T; Macrophages; Medical prognosis; Memory cells; Metastases; Metastasis; Microenvironments; Mutants; Mutation; Mutation - genetics; NF-κB protein; Prognosis; Proteins; Proto-Oncogene Proteins p21(ras) - genetics; Proto-oncogenes; Radiation therapy; Relaxin; Ribonucleic acid; RNA; Serum levels; Signal transduction; Survival analysis; T cell receptors; Tumor Microenvironment; Tumor-infiltrating immune cells; Tumor-infiltrating lymphocytes; Tumors; China; KRAS mutation; Tumor-infiltrating immune cells; Immunosuppression; Colorectal cancer
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-020-02638-9

KRAS gene is the most common type of mutation reported in colorectal cancer (CRC). KRAS mutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated. 535 CRC patients were used to compare the expression of immune-related genes (IRGs) and the abundance of tumor-infiltrating immune cells (TIICs) in the tumor microenvironment between KRAS-mutant and KRAS wild-type CRC patients. An independent dataset included 566 cases of CRC and an in-house RNA sequencing dataset were served as validation sets. An in-house dataset consisting of 335 CRC patients were used to analyze systemic immune and inflammatory state in the presence of KRAS mutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction in KRAS-mutant CRC patients was established and validated. NF-κB and T-cell receptor signaling pathways were significantly inhibited in KRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased in KRAS-mutant CRC. Prognosis correlated with enhanced Tregs, macrophage M1 and activated CD4 memory T cell and was validated. Serum levels of hypersensitive C-reactive protein (hs-CRP), CRP, and IgM were significantly decreased in KRAS-mutant compared to KRAS wild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes. KRAS mutation in CRC was associated with suppressed immune pathways and immune infiltration. The aberrant immune pathways and immune cells help to understand the tumor immune microenvironments in KRAS-mutant CRC patients.