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Open Access 01-12-2022 | Glioblastoma | Research

Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer

Authors: Kunjian Lei, Min Luo, Zewei Tu, Shigang Lv, Junzhe Liu, Chuandong Gong, Minhua Ye, Miaojing Wu, Yilei Sheng, Xiaoyan Long, Jingying Li, Xingen Zhu, Kai Huang

Published in: Cancer Cell International | Issue 1/2022

Abstract

Background

The p21-activated kinase (PAK) family (PAKs) plays a key role in the formation and development of human tumors. However, a systematic analysis of PAKs in human cancers is lacking and the potential role of PAKs in cancer immunity has not been explored.

Methods

We used datasets from in The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression database (GTEx).

Results

Based on TCGA datasets most PAKs show noteworthy differences in expression between tumors and corresponding normal tissues or across different tumor tissues. Patients with high expression of PAKs often show a worse prognosis. However, copy number variation, mutation, and DNA methylation of PAKs have limited impact on tumor development. Further analysis showed that the impact of PAKs on immunity varies with the type of tumor and the respective tumor microenvironment. PAK1 and PAK4 may be stronger predictors of immune characteristics, and are more suitable as drugs and molecular therapeutic targets. Furthermore, Cox regression analysis revealed that a PAK gene signature could be used as an independent prognostic factor for lower grade glioma (LGG) and glioblastoma (GBM). Gene set enrichment analysis (GSEA) analysis indicated that PAK genes may affect the occurrence and development of GBM through the PI3K signaling pathway. Further experiments verified that PAK1 and AKT1 have a significant interaction in GBM cells, and inhibiting the overactivation of PAK1 can significantly inhibit the proliferation of GBM cells.

Conclusions

Our study provides a rationale for further research on the prognostic and therapeutic potential of PAKs in human tumors.

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Title: Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer
Authors: Kunjian Lei
Min Luo
Zewei Tu
Shigang Lv
Junzhe Liu
Chuandong Gong
Minhua Ye
Miaojing Wu
Yilei Sheng
Xiaoyan Long
Jingying Li
Xingen Zhu
Kai Huang
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Glioblastoma
Glioma
Glioma
Glioblastoma
Glioblastoma
Glioma
Published in: Cancer Cell International / Issue 1/2022
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-022-02689-6

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Abstract

Background

Methods

Results

Conclusions

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