PLEKHA4 is a prognostic biomarker and correlated with immune infiltrates in glioma
Authors: Zhang Wei , Li Liu , Bian Piaopiao , Luo Qiuping , Xiong Zhongtang 
Published: October 2022

Abstract
Background: Gliomas are the most common and life-threatening intracranial tumors. Immune-infiltration of the tumor microenvironment significantly affects tumor prognosis in glioma. Recently, PLEKHA4 was reported to be up-regulated in melanoma and closely associated with tumor genesis and development, but its role in glioma is poorly understood.
Methods: The expression levels of PLEKHA4 in 33 types of cancer in the TCGA (The Cancer Genome Atlas) database were collected via the UCSC Xena browser. The clinical data of glioma patients were downloaded from the TCGA database. Immunohistochemistry was used to verify PLEKHA4 expression in tumor tissues. We assessed the influence of PLEKHA4 on survival of glioma patients by survival module and GEPIA. Then, we downloaded datasets of glioma from TCGA and investigated the correlations between the clinical characteristics and PLEKHA4 expression using logistic regression. Moreover, we used TIMER to explore the collection of PLEKHA4 expression and immune infiltration level in LGG and to analyse cumulative survival in LGG. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset.
Results: The results showed that PLEKHA4 transcript levels were significantly upregulated in multiple cancer types, including gliomas. Moreover,immunohistochemical analysis verified that PLEKHA4 was overexpressed in gliomas compare to the corresponding normal tissues. We assessed the influence of PLEKHA4 on survival of glioma patients by survival module and GEPIA. Then, we downloaded datasets of gliomafrom TCGA and investigated the correlations between the clinical characteristics and PLEKHA4expression was analyzed using logistic regression. Univariable survival and multivariate cox analysis showed that increased PLEKHA4 expression significantly correlated with age, tumor grade, IDH mutation status, 1p/19q codel status and higherPLEKHA4 had shorter OS,DSS,PFI. We also used TIMER to explore the collection of PLEKHA4 expression and immune infiltration level in glioma and to evaluate cumulative survival in glioma. Specifically, PLEKHA4 expression level had significant positive correlations with infiltrating levels of B cell, CD4+ T cells, CD8+T cells, macrophages, neutrophils and DCs in glioma and upregulation of PLEKHA4 expression was significantly related to immune cell biomarkers, and immune checkpoint expression in glioma. In addition, GSEA indicated that several GO and kyoto encyclopedia of genes and genomes (KEGG) items associated with daptive immune response based on somatic recombination of immine receptors builtfrom immunoglobulin superfamily domains,JAK STAT signal pathway and cell cyclewere significantly enriched in the high PLEKHA4 expression phenotype pathway.
Conclusions: Our findings proposed that PLEKHA4 was an independent prognostic biomarker and correlated with immune infiltrates in glioma, and targeting PLEKHA4 might improve immunotherapy in glioma. Of course, these findings also need basic experiments and further clinical trials to confirm in the future.