Frontiers in Immunology (Jan 2024)

Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma

  • Jingsun Wei,
  • Jingsun Wei,
  • Jingsun Wei,
  • Xiaoxu Ge,
  • Xiaoxu Ge,
  • Xiaoxu Ge,
  • Yucheng Qian,
  • Yucheng Qian,
  • Yucheng Qian,
  • Kai Jiang,
  • Kai Jiang,
  • Kai Jiang,
  • Xin Chen,
  • Xin Chen,
  • Xin Chen,
  • Wei Lu,
  • Wei Lu,
  • Wei Lu,
  • Hang Yang,
  • Hang Yang,
  • Hang Yang,
  • Dongliang Fu,
  • Dongliang Fu,
  • Dongliang Fu,
  • Yimin Fang,
  • Yimin Fang,
  • Yimin Fang,
  • Xinyi Zhou,
  • Xinyi Zhou,
  • Xinyi Zhou,
  • Qian Xiao,
  • Qian Xiao,
  • Qian Xiao,
  • Yang Tang,
  • Yang Tang,
  • Yang Tang,
  • Kefeng Ding,
  • Kefeng Ding,
  • Kefeng Ding

DOI
https://doi.org/10.3389/fimmu.2024.1291938
Journal volume & issue
Vol. 15

Abstract

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IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p<0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD.

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