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- Title
Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients.
- 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
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
COLORECTAL cancer; SUPPRESSOR cells; CANCER patients; RAS oncogenes; IMMUNOGLOBULIN M; T cells
- Publication
Journal of Translational Medicine, 2021, Vol 19, Issue 1, p1
- ISSN
1479-5876
- Publication type
journal article
- DOI
10.1186/s12967-020-02638-9