IMR Press / JIN / Volume 22 / Issue 5 / DOI: 10.31083/j.jin2205130
Open Access Original Research
PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas
Xin Gao1,2,†Yukun Liu2,†Shunming Hong3,†Hui Yang1,2Bing Guan4,*Xiaodong Ma2,*
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1 Medical School of Chinese PLA, 100853 Beijing, China
2 Department of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, 100853 Beijing, China
3 Department of Neurosurgery, The Third Medical Centre, Chinese PLA General Hospital, 100853 Beijing, China
4 Health Economics Department, Chinese PLA General Hospital, 100853 Beijing, China
*Correspondence: (Bing Guan); (Xiaodong Ma)
These authors contributed equally.
J. Integr. Neurosci. 2023, 22(5), 135;
Submitted: 28 January 2023 | Revised: 18 March 2023 | Accepted: 22 March 2023 | Published: 24 August 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Glioma is the most common intracranial malignancy. Immune-infiltration and tumour stemness are associated with the prognosis of glioma. Although pleckstrin homology containing family A, number 4 (PLEKHA4) is widely expressed in various human cancers, its role in glioma remains unclear. Methods: We examined the features and clinical significance of PLEKHA4 in gliomas by analysing relevant data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. Gene set enrichment analysis (GSEA) was performed to determine the possible functions and pathways involving PLEKHA4 in glioma. The relationship between PLEKHA4 expression and the degree of oncogenic dedifferentiation was analysed using stemness scores (ss) calculated from epigenetic and transcriptomic features. We also explored the relationship between PLEKHA4 expression and immune cell infiltration in gliomas using the CIBERSORT databases. Furthermore, drug sensitivity analysis was performed using datasets from the GDSC and GTRP databases. In addition, we performed relevant in vitro experimental studies. Results: PLEKHA4 DNA hypomethylation status was associated with its high expression in glioma tissues as well as poor prognoses. Univariate and multivariate Cox analyses indicated that PLEKHA4 expression may be considered as an independent prognostic factor in patients with glioma. GSEA indicated that high PLEKHA4 expression was associated with Janus kinase (JAK)/signal transducer and activator of transcription (STAT), Wingless-Type MMTV Integration Site Family (Wnt), JUN N-terminal kinase (JNK) signalling pathways and involved in apoptotic, cytoskeletal, and cell adhesion biological processes (BPs). In addition, increased PLEKHA4 expression was associated with higher glioma stemness scores than lower PLEKHA4 expression levels. Furthermore, the expression of PLEKHA4 was shown to be associated with glioma infiltration by CD4+ T cells, B cells, neutrophils, macrophages, and dendritic cells. Drug sensitivity analysis also showed that PLEKHA4 expression was negatively correlated with the sensitivity of several small molecule kinase inhibitors. Furthermore, in vitro experiments confirmed that PLEKHA4 knockdown inhibited the proliferation of glioma cells. Conclusions: PLEKHA4 is highly expressed in glioma tissues and correlated with tumour stemness, immune cell infiltration and proliferation, suggesting its potential as a novel prognostic biomarker and therapeutic target in glioma.

prognostic biomarkers
immune cell infiltration
tumour stemness
drug sensitivity
Fig. 1.
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