PFKP Mediates Breast Cancer Metastasis Through Altered Glycolysis

TL;DR

This study finds that PFKP, a glycolysis-related gene, is linked to breast cancer metastasis and could help predict poor patient outcomes.

Contribution

The study identifies PFKP as a novel driver of breast cancer metastasis through altered glycolysis and hypoxia pathways.

Findings

PFKP is significantly upregulated in metastatic breast tumors and correlates with glycolysis-related genes.

Higher PFKP expression is associated with poor survival and acts as a potential prognostic marker.

PFKP is negatively correlated with ER/PR/HER2 status and shows strong predictive value (AUC > 71%).

Abstract

Background

Despite recent breakthroughs in genetic profiling, breast cancer metastasis remains a considerable challenge affecting treatment and overall patient survival. Therefore, the discovery of target alternatives to restrain metastasis is urgently needed. In the current study, we aimed to identify novel targets driving metastasis and elucidate the underlying mechanisms.

Methods

We initially identified differentially expressed genes between primary breast tumors and metastatic breast cancer patients using datasets from the Gene Expression Omnibus (GEO) database. Subsequently, we validated these findings by examining the changes in gene expression and their direction in external datasets. Furthermore, we identified the significantly enriched pathways associated with gene expression. We analyzed PFKP expression patterns in 100 samples (normal, primary breast tumor, and metastasis) using quantitative real-time polymerase chain reaction (qRT-PCR), and survival analyses were performed.

Results

We identified 34 differentially expressed genes in metastatic breast tumors, with CCDC6, PKIA, UACA, and PFKP significantly upregulated (p < 0.05). PFKP was highly expressed in metastasis, negatively correlated with ER/PR/HER2 status, and linked to glycolysis-related genes (ENO1, PGM1, LDHB, and PGK1). Gene set enrichment analysis (GSEA) highlighted its role in glucose metabolism, hypoxia, and angiogenesis. qRT-PCR confirmed PFKP (p < 0.001) and Ki67 (p < 0.001) upregulation in 100 breast cancer samples. PFKP correlated with Ki67, and receiver operating characteristic (ROC) analysis (area under the curve (AUC) > 71%) indicated a strong predictive value. Higher PFKP expression was associated with poor survival, supporting its role as a prognostic marker.

Conclusion

The current study showed that PFKP promotes tumor metastasis through hypoxia-mediated altered glycolysis and can be a potential prognostic marker used to identify breast cancer metastasis.

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