Comprehensive Analysis of the Prognostic Implications and Functional Exploration of PAK Gene Family in Human Cancer

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2022 Sep 5

PMID 36064705

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

Affiliations

Soon will be listed here.

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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