Identification of prognostic biomarkers among ICAMs in the breast cancer microenvironment

Abstract

BACKGROUND: Intercellular adhesion molecules (ICAMs) in the tumor microenvironment are closely related to immunity and affect the prognosis of cancer patients. OBJECTIVE: The aim of our study is to explore the correlation between ICAM expression, mutation, methylation and immunity and their prognostic value in breast cancer (BC) is not clear. METHODS: Online databases and tools such as UALCAN, COSMIC, cBioPortal, MethSurv, PrognoScan, Kaplan-Meier Plotter, GSCA and TIMER were utilized in this study. RESULTS: We found that the mRNA and protein expression levels of ICAM1 were upregulated in triple-negative breast cancer (TNBC) compared with normal tissues, and TNBC patients with high expression of ICAM1 had better overall survival (OS) and recurrence-free survival (RFS). The main types of ICAM1 gene variants were missense mutation and amplification, and ICAM1 showed a lower level of methylation in TNBC cancer tissues than in normal tissues, which was contrary to the high expression levels of ICAM1 mRNA and protein. Next, the function of ICAM1 was mainly related to the activation of apoptosis, epithelial-mesenchymal transition (EMT) and inhibition of the androgen receptor (AR) and estrogen receptor (ER) pathways. Meanwhile, functional pathway enrichment results showed that ICAM1 was also involved in the immune regulation process of BC. Furthermore, the expression of ICAM1 was positively associated with 6 types of tumor-infiltrating immune cells (CD8+ T cells, CD4+ T cells, B cells, neutrophils, macrophages and dendritic cells) and was also positively related to the expression of programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA4). CONCLUSIONS: Our research indicated that ICAM1 was likely to be a potential therapeutic target in TNBC.