Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer

Abstract

Background:Phosphoglycerate kinase-1 (PGK1) has been recently documented in various malignancies; however, the molecular mechanisms of the variable PGK1 expression and its clinical significance in terms of survival status remain unclear.Methods:Real-time quantitative PCR (real-time qPCR) and western blotting were used to verify PGK1 expression in 46 fresh breast cancer tissues and matched normal tissues. A tissue microarray (TMA) comprising 401 breast cancer tissues and 123 matched normal tissues was investigated by immunohistochemistry for PGK1 expression. Then, the correlation between PGK1 expression and the clinicopathologic features was analysed.Results:PGK1 mRNA and protein expression were significantly increased in breast cancer tissues compared with that in normal breast tissues. High PGK1 expression was significantly associated with higher histologic grade (P=0.009) and positive status of ER (P=0.004), Her-2 (P=0.026) and P53 (P=0.012). High levels of PGK1 expression were associated with worse overall survival (OS, P=0.02). Furthermore, patients who underwent paclitaxel chemotherapy with high levels PGK1 expression had shorter OS than did those with low levels of PGK1 expression (P<0.001). Multivariate analysis indicated that PGK1 (P=0.001) was an independent predictor in the patients treated with paclitaxel.Conclusions:PGK1 is a prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer.

Quantitative Global Proteome and Lysine Succinylome Analyses Reveal the Effects of Energy Metabolism in Renal Cell Carcinoma

“…PGK1 is also believed to participate in tumorigenesis, autophagy, and cancer metastasis . As a predictor of poor survival and a prognostic biomarker of resistance to chemotherapeutics, PGK1 is overexpressed in many malignancies, including breast cancer, liver cancer, and gastric cancer . Recent research has demonstrated that hypoxic stress, EGFR activation, or the expression of K‐Ras G12V or B‐Raf V600E results in the ERK1/2‐dependent phosphorylation of PGK1 at S203, leading to PIN1‐dependent PGK1 cis – trans isomerization, the binding of PGK1 to the TOM complex, and subsequently the mitochondrial translocation of PGK1 …”

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

“…In our surgical samples we have identified three distinct isoforms of PGK1 all increased with respect to the normal tissues. Many types of cancers, including those of the breast [47], the colon [48], the liver [49] and others, have been shown to exhibit an increased expression of PGK1. Indeed, it has been demonstrated that, in addition to its role as a glycolytic enzyme, PGK1 may act as a promoter of cancer progression and induce chemoresistance for some type of drugs [47,48].…”

The Clinical Kinase Index: Prioritizing Understudied Kinases as Targets for the Treatment of Cancer

“…317/624 kinases were shown to correlate with survival in at least two cancers (Figure 3B). The kinases with the highest survival scores have been well described in the literature as predictive and prognostic biomarkers in multiple cancers; notably PGK1, PLK1 , and AURKA [49-51] . Less studied kinases such as ALPK3 (Tdark) (Figure S4) and SPEG (Tbio) also were shown to correlate with survival in 6 cancer cohorts (Supplemental table 4).…”