Prognostic Roles of Phosphofructokinase Platelet in Clear Cell Renal Cell Carcinoma and Correlation with Immune Infiltration

Abstract

Background

Abnormal expression of phosphofructokinase platelet (PFKP) has been reported in various cancer types. However, the role of PFKP in clear cell renal cell carcinoma (ccRCC) remains unclear.

Methods

In this study, the PFKP expression levels in various cancers were systemically described by integrating multiple kinds of publicly available databases. The relationship between PFKP expression and clinical prognosis of ccRCC patients was analyzed based on the TCGA database. Furthermore, PFKP-related genes and the top 10 hub genes were identified. The enrichment analysis, PPI network, and the relationship between PFKP and tumor-infiltrating immune cells were conducted to explore why PFKP was associated with clinical outcomes in ccRCC patients.

Results

PFKP was significantly highly expressed in kidney cancer, especially in ccRCC. Moreover, patients with low expression of PFKP were correlated with poor 5-year and 10-year overall survival (OS) (P < 0.05). Low PFKP expression was a risk factor associated with decreased OS in subgroups including males, females, grade 3–4, and stage III–IV (all P < 0.05). GO and KEGG enrichment analyses showed that 10 hub genes were mainly enriched in the tumor immune response. Finally, PFKP expression level was highly correlated with the infiltration of B cell, CD8⁺ T cell, CD4⁺ T cell, macrophage, neutrophil, and dendritic cell.

Conclusion

In short, our findings suggested that PFKP is highly expressed in ccRCC significantly and facilitated tumor immune response which in turn associated with a good prognosis.

Keywords:

• phosphofructokinase platelet
• clear cell renal cell carcinoma
• prognosis
• biological function enrichment analyses
• tumor immune infiltrating cells

Abbreviations

CCLE, Cancer cell line encyclopedia; ccRCC, clear cell renal cell carcinoma; cRCC, chromophobe renal cell carcinoma; DEGs, differential expression genes; DFS, disease-free survival; GEO, Gene Expression Omnibus; GEPIA, Gene Expression Profiling Interactive Analysis; GO, Gene Ontology; HPA, Human Protein Atlas; KEGG, Kyoto Encyclopedia of Genes and Genomes; OS, overall survival; OSCC, oral squamous cell carcinoma; PFKP, phosphofructokinase platelet; PPI, protein-protein interaction; pRCC, papillary renal cell carcinoma; RCC, Renal cell carcinoma; TCGA, The Cancer Genome Atlas; TIICs, tumor immune infiltrating cells.

Data Sharing Statement

Publicly available datasets were analyzed in this study. The data can be found in the GEO, TCGA, Oncomine, GEPIA, CCLE, HPA databases, Kaplan-Meier Plotter website, and Tumor Immune Estimation Resource platform.

Ethics Approval and Informed Consent

Several gene expression data and clinical characteristics of patients were publicly available. Therefore, there was no requirement for ethics committee approval.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors declare no competing interests.

Additional information

Funding

This study in the authors’ laboratory was supported by grants from the National Natural Science Foundation of China (Nos. 81970648) and International Cooperation Project of the Department of Science and Technology of Jilin Province (Nos. 20180101162JC and 20190701049GH).