- Academic Editor
†These authors contributed equally.
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