Abstract
Objective Phosphoglycerate kinase 1 (PGK1) is an essential enzyme in the process of glycolysis and mitochondrial metabolism. Herein, we conducted a systematic analysis to uncover the clinical implication of PGK1 deregulation in breast cancer. Methods Expression pattern and prognostic significance of PGK1 were comprehensively assessed across pan-cancer based on RNA-seq profiles from the TCGA project. Associations of PGK1 with immunological features in the tumor microenvironment (immune checkpoints, immune response predictors (tumor mutation burden (TMB) and microsatellite instability (MSI)), and tumor-infiltrating immune cells) were systematically analyzed. The role of PGK1 in the prediction of breast cancer prognosis was also evaluated. GSEA was presented for investigating biological pathways involved in PGK1. Results PGK1 was specifically overexpressed in most of cancer types, including breast cancer. High PGK1 expression was indicative of undesirable overall survival, progression-free interval, disease-specific survival, and disease-free interval for various cancers. Furthermore, high PGK1 levels exhibited prominent correlations to immune checkpoints and high response to immunotherapy across pan-cancer. Notably, ROC curves confirmed that PGK1 can robustly predict breast cancer prognosis. Furthermore, PGK1 might shape an inflamed tumor microenvironment following the evidence that PGK1 was positively correlated to the abundance levels of tumor-infiltrating immune cells such as CD8+ T cell and NK cell in breast cancer. GSEA results revealed that PGK1 participated in metabolism and carcinogenic pathways. Conclusion Collectively, PGK1 was capable of robustly predicting the prognosis and response to cancer immunotherapy in breast cancer.
Highlights
Breast cancer represents the dominating cause of cancerrelated deaths among women [1]
Through the TIMER2.0 web server, this study presented the differential expression of Phosphoglycerate kinase 1 (PGK1) in normal and tumor tissue specimens across pan-cancer
Through the Survival Map module of the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) web server, we observed that PGK1 was a risk factor of BRCA, CESC, ESCA, HNSC, LIHC, and SARC prognosis while PGK1 was a protective factor of KIRC prognosis (Figure 1(c))
Summary
Breast cancer represents the dominating cause of cancerrelated deaths among women [1]. This malignancy is mainly classified as Normal-like, Luminal A, Luminal B, HER2enriched, and Basal-like subtypes. Several clinical trials of ICIs have focused on the effects of CTLA4 and PD1/PDL1 inhibitors on breast cancer [6,7,8]. These ICIs are less effective as a single agent in breast cancer, partly due to low infiltration levels of tumor-infiltrating lymphocytes [9]. Strategies to improve immune response in breast cancer through combination with chemotherapy
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