PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas
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. M...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2023-08-01
|
| Series: | Journal of Integrative Neuroscience |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/JIN/22/5/10.31083/j.jin2205130 |
| _version_ | 1797677929088417792 |
|---|---|
| author | Xin Gao Yukun Liu Shunming Hong Hui Yang Bing Guan Xiaodong Ma |
| author_facet | Xin Gao Yukun Liu Shunming Hong Hui Yang Bing Guan Xiaodong Ma |
| author_sort | Xin Gao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T22:52:12Z |
| format | Article |
| id | doaj.art-eea71dd3a11d45b19ab14b530c335588 |
| institution | Directory Open Access Journal |
| issn | 0219-6352 |
| language | English |
| last_indexed | 2024-03-11T22:52:12Z |
| publishDate | 2023-08-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Journal of Integrative Neuroscience |
| spelling | doaj.art-eea71dd3a11d45b19ab14b530c3355882023-09-22T02:49:15ZengIMR PressJournal of Integrative Neuroscience0219-63522023-08-0122513510.31083/j.jin2205130S0219-6352(23)00542-9PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of GliomasXin Gao0Yukun Liu1Shunming Hong2Hui Yang3Bing Guan4Xiaodong Ma5Medical School of Chinese PLA, 100853 Beijing, ChinaDepartment of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, 100853 Beijing, ChinaDepartment of Neurosurgery, The Third Medical Centre, Chinese PLA General Hospital, 100853 Beijing, ChinaMedical School of Chinese PLA, 100853 Beijing, ChinaHealth Economics Department, Chinese PLA General Hospital, 100853 Beijing, ChinaDepartment of Neurosurgery, The First Medical Centre, Chinese PLA General Hospital, 100853 Beijing, ChinaBackground: 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.https://www.imrpress.com/journal/JIN/22/5/10.31083/j.jin2205130gliomaplekha4prognostic biomarkersmethylationimmune cell infiltrationtumour stemnessdrug sensitivity |
| spellingShingle | Xin Gao Yukun Liu Shunming Hong Hui Yang Bing Guan Xiaodong Ma PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas Journal of Integrative Neuroscience glioma plekha4 prognostic biomarkers methylation immune cell infiltration tumour stemness drug sensitivity |
| title | PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas |
| title_full | PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas |
| title_fullStr | PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas |
| title_full_unstemmed | PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas |
| title_short | PLEKHA4 is Associated with Tumour Microenvironment, Stemness, Proliferation and Poor Prognosis of Gliomas |
| title_sort | plekha4 is associated with tumour microenvironment stemness proliferation and poor prognosis of gliomas |
| topic | glioma plekha4 prognostic biomarkers methylation immune cell infiltration tumour stemness drug sensitivity |
| url | https://www.imrpress.com/journal/JIN/22/5/10.31083/j.jin2205130 |
| work_keys_str_mv | AT xingao plekha4isassociatedwithtumourmicroenvironmentstemnessproliferationandpoorprognosisofgliomas AT yukunliu plekha4isassociatedwithtumourmicroenvironmentstemnessproliferationandpoorprognosisofgliomas AT shunminghong plekha4isassociatedwithtumourmicroenvironmentstemnessproliferationandpoorprognosisofgliomas AT huiyang plekha4isassociatedwithtumourmicroenvironmentstemnessproliferationandpoorprognosisofgliomas AT bingguan plekha4isassociatedwithtumourmicroenvironmentstemnessproliferationandpoorprognosisofgliomas AT xiaodongma plekha4isassociatedwithtumourmicroenvironmentstemnessproliferationandpoorprognosisofgliomas |