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Open Access 01-12-2021 | Colorectal Cancer | Research

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

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

Published in: Journal of Translational Medicine | Issue 1/2021

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Title: Immune landscape and prognostic immune-related genes in KRAS-mutant colorectal cancer patients
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
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Colorectal Cancer
Colorectal Cancer
Published in: Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-020-02638-9

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