Abstract
Background Quinolinic acid phosphoribosyltransferase (QPRT) is a rate-limiting enzyme that encodes the uronic acid pathway, which is involved in cell cycle progression and cancer cell metabolism. Some studies have demonstrated the progrowth effect of QPRT on breast cancer (BRCA) tumour cells, but its mechanism of action requires further exploration. Methods We investigated the expression of QPRT and the prognosis of patients with different tumours by performing a pan-cancer analysis of QPRT. Prognostic values for overall survival (OS) were determined using uni- and multivariate Cox proportional hazard analyses. The prognostic survival of patients with a different pathological staging of BRCA and with QPRT high and low expression was also analysed. We also explored the relevant pathways by which QPRT affected BRCA tumorigenesis by gene set enrichment analysis (GSEA) and western blotting. The impact of QPRT on the PI3K/Akt pathway was also evaluated. Results Pan-cancer analysis revealed significant QPRT expression in pan-cancer and correlated with prognosis in most tumour patients. QPRT was also highly expressed in BRCA when patients had poor prognoses, and its expression was associated with different pathological BRCA subtypes. GSEA revealed an association between BRCA progression and the cell cycle and the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway, and this association was confirmed by western blotting. Conclusion QPRT is highly expressed in breast cancer and particularly in HER2 breast cancer. Upregulated QPRT expression is an independent predictor of breast cancer prognosis and promotes breast cancer progression by activating the PI3K/Akt signalling pathway.
Highlights
As of 2020, invasive breast cancer (BRCA) (2.26 million cases) remains one of the most commonly diagnosed cancer types worldwide [1] and is the leading cause of cancer death in women aged 20–59 years [2]
33 tumour samples were obtained from the TCGA dataset, RNA sequencing data for 21 tumour cell lines were obtained from the CCLE dataset, and expression profile data were obtained for 27 cancer and paracancer tissues by integrating the TCGA and Genotype-Tissue Expression (GTEx) datasets. e expression matrices of GSE46563 and GSE59246 were obtained from the GEO database
High Quinolinic acid phosphoribosyltransferase (QPRT) expression was significantly associated with poor overall survival (OS) prognosis in patients with BRCA, KIRP, LGG, SKCM, and UVM, and the relationship between high and low QPRT expressions and patients with each tumour was further confirmed using KM curves (Figures 2(a) and 2(b))
Summary
As of 2020, invasive breast cancer (BRCA) (2.26 million cases) remains one of the most commonly diagnosed cancer types worldwide [1] and is the leading cause of cancer death in women aged 20–59 years [2]. Studies have shown that high expression of NAMPT is related to the Journal of Oncology aggressive biological characteristics of BRCA [14] and can regulate the PI3K-AKT signalling pathway and promote tumour cell proliferation [15]. Quinolinic acid phosphoribosyltransferase (QPRT) is a rate-limiting enzyme that encodes the uronic acid pathway, which is involved in cell cycle progression and cancer cell metabolism. E prognostic survival of patients with a different pathological staging of BRCA and with QPRT high and low expression was analysed. GSEA revealed an association between BRCA progression and the cell cycle and the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway, and this association was confirmed by western blotting. Upregulated QPRT expression is an independent predictor of breast cancer prognosis and promotes breast cancer progression by activating the PI3K/Akt signalling pathway
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