Frontiers in Pharmacology (Apr 2022)
High Expression of RAI14 in Triple-Negative Breast Cancer Participates in Immune Recruitment and Implies Poor Prognosis Through Bioinformatics Analyses
Abstract
Objective: The purpose of current research is to explore the function of retinoic acid-induced protein 14 (RAI14), being a reciprocal protein of carboxypeptidase N1 (CPN1), and as a biomarker for prognosis and immunoregulatory effects in breast cancers.Methods: Interacting proteins of CPN1 were characterized by co-immunoprecipitation (CO-IP) and mass spectrometry. We evaluated RAI14 expression and related clinical prognosis based on bioinformatics methods. The level of relevance between RAI14 and infiltrating immune cells biomarkers was investigated by using TIMER and certificated by immunohistochemical staining and cytology experiments.Results: RAI14 is an interacting protein of CPN1. Higher RAI14 expression in TNBC was significantly correlated with poor prognosis in TNBC, especially (RFS: HR = 1.32, p = 0.015; DFS: HR = 1.18, p = 0.035). The estrogen receptor (ER), P53 status, and histological types and triple-negative status were observed and correlated with RAI14 expression. Moreover, the level of RAI14 was positive in relation with the expression of CD163 (M2 macrophages marker, r = 0.393, p = 1.89e-06) and PD-1 (T-cell exhaustion marker, r = 0.626, p = 4.82e-03), indicating RAI14 levels were mainly related to M2 macrophages and T-cell exhaustion infiltration in TNBC. Furthermore, CPN1 overexpression was accompanied by RAI14 and PD-L1 upregulation, and a correlation was found among them.Conclusions: RAI14 is a potential downstream molecule of CPN1, which may be a potential prognostic biomarker and identification of an immunosuppressive tumor microenvironment in TNBC.
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