Comprehensive analysis of the immune implication of FABP4 in colon adenocarcinoma

PLoS One. 2022 Oct 20;17(10):e0276430. doi: 10.1371/journal.pone.0276430. eCollection 2022.

Abstract

Background: Fatty acid-binding protein 4 (FABP4) has been reported to be associated with tumor progress and poor prognosis in various cancers. However, the relationship between FABP4 expression and tumor immunity in colon adenocarcinoma (COAD) is still poorly understood.

Methods: FABP4 mRNA expression was analyzed using The Cancer Genome Atlas (TCGA)-COAD data. FABP4 protein staining was performed by immunohistochemistry (IHC) staining in our 10 paired COAD samples and corresponding adjacent noncancerous tissues. The association between FABP4 and immune cell infiltration was evaluated by Tumor Immune Estimation Resource (TIMER) database. FABP4 coexpressed genes were identified based on Cancer Cell Line Encyclopedia (CCLE) database, which were employed for further enrichment analysis. FABP4 related immunomodulators was identified by Tumor and Immune System Interaction Database (TISIDB) database, and a prognostic risk signature was constructed based on FABP4-related immunomodulators using stepwise Cox regression analysis. A nomogram consists of FABP4 related immunomodulators signature and clinical parameters was developed to predict the overall survival (OS).

Results: In TCGA data, we found that the decreased FABP4 mRNA expression in COAD samples compared with normal samples, and low FABP4 mRNA expression was associated with B cells, CD4+ T cells, CD8+ T cells, myeloid dendritic cells, macrophages, and neutrophils. In our 10 paired samples, the protein levels of COAD were lower in all COAD tissues than in their adjacent noncancerous tissues. Functional enrichment analysis revealed that FABP4 coexpressed genes were mostly enriched in immune-related pathways. Based on 54 FABP4-related immunomodulators, a 2-gene FABP4-related prognostic risk signature was developed, and the signature stratified the patients into the high-risk and low-risk groups with statistically different survival outcomes. The Nomogram consists of the prognostic signature and clinical parameters had a certain predictability for prognosis of COAD patients.

Conclusion: These findings suggest that FABP4 is associated with 2-gene immune signature which also correlate with the prognosis of COAD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma* / pathology
  • Biomarkers, Tumor / genetics
  • Colonic Neoplasms* / pathology
  • Fatty Acid-Binding Proteins / genetics
  • Gene Expression Profiling
  • Humans
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • Fatty Acid-Binding Proteins
  • FABP4 protein, human

Grants and funding

This work was supported by The General Project of Chongqing Natural Science Foundation, Chongqing Science and Technology Commission, China (cstc2021jcyj-msxmX0153), and The Kuanren Talents Program of The Second Affiliated Hospital of Chongqing Medical University (kryc-yq-2110). Funders play a role in data collection and analysis.