Immune checkpoint CD155 promoter methylation profiling reveals cancer-associated behaviors within breast neoplasia

Abstract

BACKGROUND: CD155 immune checkpoint has recently emerged as a compelling immunotherapeutic target. Epigenetic DNA methylation changes are recognized as key molecular mechanisms in cancer development. Hence, the identification of methylation markers that are sensitive and specific for breast cancer may improve early detection and predict prognosis. We speculate that CD155 promoter methylation can be a valuable epigenetic biomarker, based upon strong indications for its immunoregulatory functions.METHODS: Methylation analyses were conducted on 14 CpGs sites in the CD155 promoter region by bisulfite pyrosequencing. To elucidate the related gene expression changes, a transcriptional study using RT-qPCR was performed. Statistical analyses were performed to evaluate correlations of CD155 methylation profiles with mRNA expression together with clinical-pathological features, prognosis and immune infiltrate.RESULTS: CD155 promoter methylation profile was significantly associated with SBR grade, tumor size, molecular subgroups, HER2 and hormonal receptors expression status. Low CD155 methylation rates correlated with better prognosis in univariate cox proportional hazard analysis, and appeared as an independent survival predictor in cox-regression multivariate analysis. Further, methylation changes at CD155 specific CpG sites were consistent with CD155 membranous mRNA isoform expression status.Statistical analyses also showed a significant association with immune Natural Killer cell infiltrate when looking at the CpG7, CpG8, CpG9 and CpG11 sites. CONCLUSION: Altogether, our results contribute to a better understanding of the impact of CD155 immune checkpoint modality expression in breast tumors, revealing for the first time that specific CpG sites from CD155 promoter may be a potential biomarker in breast cancer monitoring.

Blockade of CD155 and Interleukin-6 Suppresses Breast Cancer Cell Growth

“…28,32 Moreover, the researchers found that the methylation at the CpG site of the CD155 promoter is directly related to cancer progression and tumor size. 33 However, there is little information about the role of this biomarker (CD155) in breast cancer. 34 Our findings revealed that the expression of this biomarker increases in breast cancer.…”

Bioinformatic analysis and experimental validation identified DNA methylation–Related biomarkers and immune-cell infiltration of atherosclerosis

“…In another study on hepatocellular carcinoma, LOXL3 was first reported to link with immune infiltrates. A statistical analysis has been applied to explore the relationship between the LOXL3 expression and the infiltration of multiple immune cells ( Wang N. et al, 2021 ; Triki et al, 2022 ). The association between target gene and immune-cell infiltration can be further verified experimentally, with quantitative multiplex immunohistochemistry or immunohistochemistry staining ( Wang Y. et al, 2021 ; Gatti et al, 2021 ).…”