关键词: Peptidyl-prolyl isomerase F (PPIF) immune lung adenocarcinoma (LUAD) mitophagy prognosis

来  源:   DOI:10.21037/tlcr-24-344   PDF(Pubmed)

Abstract:
UNASSIGNED: Lung adenocarcinoma (LUAD) is among the most prevalent malignancies worldwide, with unfavorable treatment outcomes. Peptidyl-prolyl isomerase F (PPIF) is known to influence the malignancy traits of tumor progression by modulating the bioenergetics and mitochondrial permeability in cancer cells; however, its role in LUAD remains unclear. Our study seeks to investigate the clinical significance, tumor proliferation, and immune regulatory functions of PPIF in LUAD.
UNASSIGNED: The expression of PPIF in LUAD tissues and cells was assessed using bioinformatics analysis, immunohistochemistry (IHC), and Western blotting. Survival curve analysis was conducted to examine the prognostic association between PPIF expression and LUAD. The immunomodulatory role of PPIF in LUAD was assessed through the analysis of PPIF expression and immune cell infiltration. A series of gain- and loss-of-function experiments were conducted on PPIF to investigate its biological functions in LUAD both in vitro and in vivo. The mechanisms underlying PPIF\'s effects on LUAD were delineated through functional enrichment analysis and Western blotting assays.
UNASSIGNED: PPIF exhibited overexpression in LUAD tissues compared to normal controls. Survival curve analysis revealed that patients with LUAD exhibiting higher PPIF expression demonstrated decreased overall survival and a shorter progression-free interval. PPIF was implicated in modulating immune cell infiltration, particularly in regulating the T helper 1-T helper 2 cell balance. Functionally, PPIF was discovered to promote tumor cell proliferation and advance cell-cycle progression. Furthermore, PPIF could impede mitophagy by targeting the FOXO3a/PINK1-Parkin signaling pathway.
UNASSIGNED: The findings of this study indicate that the prognosis-related gene PPIF may have a significant role in the regulation of LUAD cell proliferation, tumor-associated immune cell infiltration, and mitophagy, and thus PPIF may be a promising therapeutic target of LUAD.
摘要:
肺腺癌(LUAD)是全球最常见的恶性肿瘤之一,不利的治疗结果。已知肽基氨酰异构酶F(PPIF)通过调节癌细胞的生物能学和线粒体通透性来影响肿瘤进展的恶性特征;然而,其在LUAD中的作用尚不清楚。我们的研究旨在探讨临床意义,肿瘤增殖,以及PPIF在LUAD中的免疫调节功能。
使用生物信息学分析评估了PPIF在LUAD组织和细胞中的表达,免疫组织化学(IHC),和西方印迹。进行生存曲线分析以检查PPIF表达与LUAD之间的预后关联。通过分析PPIF表达和免疫细胞浸润来评估PPIF在LUAD中的免疫调节作用。对PPIF进行了一系列功能增益和功能丧失实验,以研究其在LUAD中的体外和体内生物学功能。通过功能富集分析和Western印迹分析,描述了PPIF对LUAD影响的潜在机制。与正常对照相比,
PPIF在LUAD组织中表现出过表达。生存曲线分析显示,表现出较高PPIF表达的LUAD患者表现出总体生存期降低和无进展间隔较短。PPIF与调节免疫细胞浸润有关,特别是在调节T辅助1-T辅助2细胞平衡。功能上,发现PPIF可促进肿瘤细胞增殖并促进细胞周期进程。此外,PPIF可能通过靶向FOXO3a/PINK1-Parkin信号通路阻止线粒体自噬。
这项研究的结果表明,预后相关基因PPIF可能在调节LUAD细胞增殖中起重要作用,肿瘤相关免疫细胞浸润,和线粒体自噬,因此PPIF可能是LUAD的一个有希望的治疗靶点。
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