Prognostic value of PLEKHA4 and its correlation with tumor-infiltrating immune cells in breast cancer: a comprehensive study based on bioinformatics and clinical analysis validation.
Liu Li, Zewen Feng, Ye Zhao, Boan Lai, Qingxin Zhang, Zhongtang Xiong, Wei Zhang
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引用次数: 0
Abstract
Background: Pleckstrin homology containing family A, number 4 (PLEKHA4) plays a role in a number of biological processes in human cells, including cell polarization, growth, and proliferation. However, the relationship between PLEKHA4 expression and survival in breast cancer (BC) remains unclear. The aim of this study is to investigate the potential of PLEKHA4 as a prognostic indicator in BC.
Methods: We obtained gene expression profiles of BC and normal tissues from the Tumor Immune Estimation Resource (TIMER), UALCAN web. Immunohistochemistry (IHC) staining was performed to investigate the protein expression and prognostic value of PLEKHA4 in BC patients. The prognostic value was analyzed using Kaplan-Meier curve analysis and Cox regression analysis in R software after downloading The Cancer Genome Atlas (TCGA) databases. The correlations between PLEKHA4 and tumor immune infiltrates were investigated via gene set variation analysis (GSVA). Signaling pathways related to PLEKHA4 expression were identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.
Results: Both bioinformatics and IHC results showed that PLEKHA4 was expressed at low levels in BC tissues compared with the adjacent tissues. Furthermore, the expression of PLEKHA4 was negatively correlated with ages (χ2=6.394, P=0.01), molecular subtype (χ2=15.606, P=0.001), lymph node metastasis (χ2=13.753, P=0.004), tumor-node-metastasis (TNM) stage (χ2=22.616, P<0.001). Kaplan-Meier curves implicated low expression of PLEKHA4 was associated with worse survival of BC patients [hazard ratio (HR) =0.46, P=0.01]. Cox regression models showed that low PLEKHA4 expression could be an independent risk factor for BC (HR =0.911, P=0.006). The results of gene set enrichment analysis (GSEA) showed that cell cycle, Notch signaling pathway, nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway, and Rho GTPases were highly enriched in the low PLEKHA4 expression group, as identified by GO and KEGG. Additionally, in BC, PLEKHA4 expression displayed a positive correlation with the infiltration of natural killer (NK) cells (P<0.001), CD8+ T cells (P<0.001), B cells (P<0.001), neutrophils (P<0.001), and dendritic cells (DCs) (P<0.001).
Conclusions: The findings indicate that PLEKHA4 is an independent prognostic biomarker associated with key signaling pathways and immune infiltration in BC. Targeting PLEKHA4 may contribute to improving immunotherapy for BC.
背景：Pleckstrin homology containing family A, number 4 (PLEKHA4)在人类细胞的一系列生物过程中发挥作用，包括细胞极化、生长和增殖。然而，PLEKHA4的表达与乳腺癌（BC）生存率之间的关系仍不清楚。本研究旨在探讨PLEKHA4作为乳腺癌预后指标的潜力：我们从 UALCAN 网络的肿瘤免疫估算资源（TIMER）中获得了 BC 和正常组织的基因表达谱。免疫组化（IHC）染色研究了PLEKHA4在BC患者中的蛋白表达和预后价值。在下载癌症基因组图谱（TCGA）数据库后，利用R软件中的Kaplan-Meier曲线分析和Cox回归分析对预后价值进行了分析。通过基因组变异分析（GSVA）研究了PLEKHA4与肿瘤免疫浸润的相关性。通过基因本体（GO）和京都基因和基因组百科全书（KEGG）富集分析确定了与PLEKHA4表达相关的信号通路：生物信息学和IHC结果显示，与邻近组织相比，PLEKHA4在BC组织中的表达水平较低。此外，PLEKHA4的表达与年龄（χ2=6.394，P=0.01）、分子亚型（χ2=15.606，P=0.001）、淋巴结转移（χ2=13.753，P=0.004）、肿瘤-结-转移（TNM）分期（χ2=22.616，P+ T细胞（PConclusions：研究结果表明，PLEKHA4是一个独立的预后生物标志物，与BC的关键信号通路和免疫浸润有关。以PLEKHA4为靶点可能有助于改善BC的免疫疗法。
期刊介绍：
Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.
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