RIBC2 expression as a potential diagnostic and prognostic biomarker associated with tumor progression and immune modulation in breast cancer

Abstract

Breast cancer remains one of the deadliest diseases around the world. This study systematically investigates the expression profile and clinical significance of RIBC2 in breast cancer. By integrating multi-omics data from public databases, such as The Cancer Genome Atlas and The Genotype-Tissue Expression project, combined with bioinformatic analyses and molecular docking simulations, we demonstrated that RIBC2 is significantly overexpressed in breast cancer tissues. Elevated RIBC2 expression was positively correlated with higher T stage, advanced pathological stage, and poorer overall survival. Functional enrichment analyses indicated that RIBC2 may facilitate tumor invasion by regulating extracellular matrix remodeling and activating the mitogen-activated protein kinase signaling pathway. Multivariate Cox regression analysis confirmed high RIBC2 expression as an independent poor prognostic factor, with its inclusion slightly increasing the area under the curve of the prognostic model from 0.762 to 0.764. Moreover, immune infiltration analysis revealed that high RIBC2 expression was associated with increased infiltration of regulatory T cells and M2-polarized macrophages, indicating a potential role in shaping an immune suppressive tumor microenvironment. Spearman correlation analysis between RIBC2 and immune checkpoints showed significant positive associations only for lymphocyte activation gene 3 protein (p<0.001, absolute correlation ≈ 0.1) and human leukocyte antigen-C (p=0.045, absolute correlation ≈ 0.08), indicating RIBC2 may selectively modulate specific immunosuppressive pathways. Drug sensitivity analysis further suggested that RIBC2 overexpression may contribute to chemotherapy resistance. The methylation level of RIBC2 was found to be significantly negatively correlated with its expression, suggesting that hypermethylation in the promoter or regulatory regions may suppress gene expression through epigenetic silencing mechanisms. Furthermore, quantitative polymerase chain reaction revealed a 4.2-fold RIBC2 upregulation in triple-negative breast cancer cells (MDA-MB-231) compared to normal mammary cells (Hs578bst), exceeding levels in luminal subtypes (MCF-7). Collectively, these findings highlight RIBC2 as a promising prognostic biomarker and provide a theoretical foundation for developing combination therapeutic strategies targeting RIBC2.

Keywords

Breast cancer / RIBC2 / Prognostic marker / Metastasis / Immunity

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