关键词: PPP4C immunotherapy lung adenocarcinoma prognosis single-cell

Mesh : Female Humans Male Adenocarcinoma of Lung / immunology therapy Biomarkers, Tumor / genetics Cell Line, Tumor Gene Expression Profiling Gene Expression Regulation, Neoplastic Immunotherapy / methods Lung Neoplasms / immunology therapy Multiomics Phosphoprotein Phosphatases / genetics Prognosis Single-Cell Analysis / methods Transcriptome Tumor Microenvironment / genetics immunology

来  源:   DOI:10.3389/fimmu.2024.1416632   PDF(Pubmed)

Abstract:
UNASSIGNED: Elevated PPP4C expression has been associated with poor prognostic implications for patients suffering from lung adenocarcinoma (LUAD). The extent to which PPP4C affects immune cell infiltration in LUAD, as well as the importance of associated genes in clinical scenarios, still requires thorough investigation.
UNASSIGNED: In our investigation, we leveraged both single-cell and comprehensive RNA sequencing data, sourced from LUAD patients, in our analysis. This study also integrated datasets of immune-related genes from InnateDB into the framework. Our expansive evaluation employed various analytical techniques; these included pinpointing differentially expressed genes, constructing WGCNA, implementing Cox proportional hazards models. We utilized these methods to investigate the gene expression profiles of PPP4C within the context of LUAD and to clarify its potential prognostic value for patients. Subsequent steps involved validating the observed enhancement of PPP4C expression in LUAD samples through a series of experimental approaches. The array comprised immunohistochemistry staining, Western blotting, quantitative PCR, and a collection of cell-based assays aimed at evaluating the influence of PPP4C on the proliferative and migratory activities of LUAD cells.
UNASSIGNED: In lung cancer, elevated expression levels of PPP4C were observed, correlating with poorer patient prognoses. Validation of increased PPP4C levels in LUAD specimens was achieved using immunohistochemical techniques. Experimental investigations have substantiated the role of PPP4C in facilitating cellular proliferation and migration in LUAD contexts. Furthermore, an association was identified between the expression of PPP4C and the infiltration of immune cells in these tumors. A prognostic framework, incorporating PPP4C and immune-related genes, was developed and recognized as an autonomous predictor of survival in individuals afflicted with LUAD. This prognostic tool has demonstrated considerable efficacy in forecasting patient survival and their response to immunotherapeutic interventions.
UNASSIGNED: The involvement of PPP4C in LUAD is deeply intertwined with the tumor\'s immune microenvironment. PPP4C\'s over-expression is associated with negative clinical outcomes, promoting both tumor proliferation and spread. A prognostic framework based on PPP4C levels may effectively predict patient prognoses in LUAD, as well as the efficacy of immunotherapy strategy. This research sheds light on the mechanisms of immune interaction in LUAD and proposes a new strategy for treatment.
摘要:
升高的PPP4C表达与患有肺腺癌(LUAD)的患者的不良预后意义相关。PPP4C在LUAD中影响免疫细胞浸润的程度,以及相关基因在临床情景中的重要性,仍然需要彻底调查。
在我们的调查中,我们利用了单细胞和全面的RNA测序数据,来自LUAD患者,在我们的分析中这项研究还将来自InnateDB的免疫相关基因的数据集整合到框架中。我们广泛的评估采用了各种分析技术;这些技术包括精确定位差异表达基因,构建WGCNA,实施Cox比例风险模型。我们利用这些方法在LUAD的背景下研究PPP4C的基因表达谱,并阐明其对患者的潜在预后价值。随后的步骤涉及通过一系列实验方法验证在LUAD样品中观察到的PPP4C表达的增强。阵列包括免疫组织化学染色,西方印迹,定量PCR,以及一系列基于细胞的测定法,旨在评估PPP4C对LUAD细胞增殖和迁移活性的影响。
在肺癌中,观察到PPP4C的表达水平升高,与较差的患者预后相关。使用免疫组织化学技术实现了LUAD标本中增加的PPP4C水平的验证。实验研究证实了PPP4C在LUAD环境中促进细胞增殖和迁移的作用。此外,在这些肿瘤中,PPP4C的表达与免疫细胞浸润之间存在相关性.预后框架,整合PPP4C和免疫相关基因,被开发并被认为是患有LUAD的个体生存的自主预测因子。该预后工具已证明在预测患者生存及其对免疫治疗干预的反应方面具有相当大的功效。
PPP4C在LUAD中的参与与肿瘤的免疫微环境密切相关。PPP4C的过表达与阴性临床结果相关,促进肿瘤增殖和扩散。基于PPP4C水平的预后框架可以有效预测LUAD患者的预后。以及免疫治疗策略的疗效。本研究揭示了LUAD的免疫相互作用机制,并提出了一种新的治疗策略。
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