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

• DOI: 10.1186/s12967-020-02638-9
• Publication Date: 2021-01-07T12:03:47Z
• Authors: Jungang Liu; Xiaoliang Huang; Haizhou Liu; Chunyin Wei; Haiming Ru; Haiquan Qin; Hao Lai; Yongsheng Meng; Guo Wu; Weishun Xie; Xianwei Mo; Caroline H. Johnson; Yawei Zhang; Weizhong Tang
• Keywords: 0303 health sciences; Research; Relaxin; R; KRAS mutation; Prognosis; Colorectal cancer; 3. Good health; Proto-Oncogene Proteins p21(ras); 03 medical and health sciences; Genes, ras; Antigens, Neoplasm; Colonic Neoplasms; Mutation; Tumor Microenvironment; Medicine; Humans; Tumor-infiltrating immune cells; Colorectal Neoplasms; Immunosuppression

AbstractBackgroundKRASgene is the most common type of mutation reported in colorectal cancer (CRC).KRASmutation-mediated regulation of immunophenotype and immune pathways in CRC remains to be elucidated.Methods535 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 betweenKRAS-mutant andKRASwild-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 ofKRASmutation. An immue risk (Imm-R) model consist of IRG and TIICs for prognostic prediction inKRAS-mutant CRC patients was established and validated.ResultsNF-κB and T-cell receptor signaling pathways were significantly inhibited inKRAS-mutant CRC patients. Regulatory T cells (Tregs) was increased while macrophage M1 and activated CD4 memory T cell was decreased inKRAS-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 inKRAS-mutant compared toKRASwild-type CRC patients. An immune risk model composed of VGF, RLN3, CT45A1 and TIICs signature classified CRC patients with distinct clinical outcomes.ConclusionsKRASmutation 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 inKRAS-mutant CRC patients.