Bioinformatics analysis reveals PIH1D1 as an important prognostic marker in breast cancer

Abstract

R2TP (Rvb1, Rvb2, Tah1, and Pih1) complex was initially discovered as a Heat shock protein 90 associated multimeric protein complex in yeast and is highly conserved in mammals. In Human R2TP complex is known by different names including RUVBL1 for Rvb1, RuvBL2 for Rvb2, RPAP3 (RNA polymerase II-associated protein 3) for Tah1 and PIH1D1 for Pih1, and known to be a specialized Co-chaperone of Hsp-90 protein. This multimeric-protein complex is involved in the assembly and maturation of several multisubunit complexes including RNA polymerase II, small nucleolar ribonucleoproteins, and complexes containing phosphatidylinositol-3-kinase-like kinases. Nevertheless, evidence in the clinical setting is scanty with respect to the expression of PIH1 domain containing 1 (PIH1D1) and its prognostic values in breast cancer (BRCA). Exploring the function of PIH1D1 in BRCA could reveal its therapeutic and translational potential in BRCA. In the current study, we analyzed PIH1D1 expression levels across cancers with the help of a bioinformatics tool and tumor immune estimation resource, and compared with normal and BRCA tissues using tumor, normal, and metastasis plot. Disease-free and overall survival analysis was done by survival plot, in gene expression profiling interactive analysis web server. Furthermore, histological analysis of PIH1D1 protein expression was done with the help of the Human Protein Atlas Database. Clusters and interaction analysis were done using cell line expression cluster toll in Human Protein Atlas. The result of our study shows that PIH1D1 expression was higher in almost all cancer groups and significantly increased in BRCA. Additionally, we found a positive statistical correlation between PIH1D1 and CD4+ and CD8+ T cell infiltration, which is an indication of the immunotherapeutic potential of PIH1D1. The expression of chemokines and receptors was shown to be significantly positively linked with Chemokine (C-C motif) ligand 14 when PIH1D1 was increased. Furthermore, the UALCAN (University of ALabama at Birmingham CANcer) data analysis results also revealed that PIH1D1 was significantly associated with tumor metastasis, menopausal status, grade, and different stages of patients with BRCA. In conclusion, the current study provides the preliminary proof of concept regarding the biomarker potential of PIH1D1. However, further in vivo and in vitro mechanistic studies in detail are required to explore the therapeutic potential of PIH1D1 in BRCA.