Abstract
Background
Protein phosphatase 1 regulatory subunit 14B (PPP1R14B) is an oncogenic gene found in a variety of tumors, but its role in the prognosis and development of kidney renal clear cell carcinoma (KIRC) remains unknown. Our study aimed to determine whether PPP1R14B could be a prognostic biomarker for KIRC and its role in the development of KIRC.
Methods
In this work, we used The Cancer Genome Atlas (TCGA) database to explore the expression of PPP1R14B in tumor tissues, its relationship with the prognosis of tumor patients, and its role in tumor occurrence and development. We validated our findings using the International Cancer Genome Consortium (ICGC) cohort, our clinical samples, and in vitro experiments.
Results
PPP1R14B was upregulated in KIRC compared to adjacent normal tissue. Moreover, multivariate analysis revealed that upregulated PPP1R14B expression was an independent risk factor for KIRC progression. High-PPP1R14B groups had shorter overall survival (OS) and disease-free survival (DFS) in TCGA and ICGC cohorts. We used Cell Counting Kit-8 (CCK8) and scratch wound healing assay to explore the proliferation and migration of KIRC cells following PPP1R14B knockdown. Our results indicated that PPP1R14B knockdown significantly reduced the proliferation and migration of KIRC cells in vitro. We also explored the possible cellular mechanisms of PPP1R14B through the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) analysis, and TISIDB analysis. The function enrich analysis revealed that PPP1R14B-related genes were mainly enriched in purine metabolism and the macromolecule catabolic process. PPP1R14B expression was associated with tumor-infiltrating immune cells (TIICs) in the TCGA cohort, and the results of single-cell RNA-seq (scRNA) further demonstrated that PPP1R14B expression was associated with the enhanced infiltration of CD8 + T lymphocytes.
Conclusion
PPP1R14B may serve as a prognostic biomarker in KIRC, affect purine metabolism, activate immune infiltration, and promote KIRC cell migration.
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Data availability
The datasets of this study were from UCSC Xena database (http://xena.ucsc.edu/), the ICGC database (https://dcc.icgc.org/), and GEO database. The author will provide the original data of RT-qPCR, CCK-8, and scratch wound healing assay to any qualified researcher without excessive retention.
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We thank Home for Researchers editorial team (www.home-for-researchers.com) for language editing service.
Funding
This work was supported by Guangxi Key Research and Development Project (Grant No. Guike AB21196022) and Guangxi Science and Technology Major Project (Grant No. Guike AA22412).
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Cheng, L., Mi, J., Zhang, J. et al. Upregulated PPP1R14B is connected to cancer progression and immune infiltration in kidney renal clear cell carcinoma. Clin Transl Oncol 26, 119–135 (2024). https://doi.org/10.1007/s12094-023-03228-z
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DOI: https://doi.org/10.1007/s12094-023-03228-z