ZP3 Expression in Pancreatic Adenocarcinoma: Its Implications for the Prognosis and Therapy.

IF 1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Protein and Peptide Letters Pub Date : 2025-01-08 DOI:10.2174/0109298665350171241204153202

Guizhen Lyu, Dongbing Li

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引用次数: 0

Abstract

Background: The role of Zona pellucida glycoprotein 3 (ZP3) is unclear in pancreatic adenocarcinoma (PAAD).

Objective: This study aimed to explore the role of ZP3 in PAAD.

Methods: A comparative analysis of ZP3 gene expression was performed to discern differences between various types of cancer and PAAD, leveraging data sourced from The Cancer Genome Atlas (TCGA). This study aimed to assess the role of ZP3 as a potential diagnostic marker for PAAD. The relationship between ZP3 levels and clinical characteristics, as well as patient outcomes, was scrutinized. Additionally, genomic enrichment analysis was carried out to uncover the underlying regulatory mechanisms associated with ZP3. The study further delved into the association of ZP3 with immune system interactions, checkpoint gene expression, Tumor Mutational Burden (TMB), microsatellite instability (MSI), and tumor stemness index (mRNAsi). The aberrant expression patterns of ZP3 in PAAD cell cultures were confirmed through the application of quantitative reverse transcription PCR (qRT-PCR) techniques.

Results: ZP3 exhibited aberrant expression in both pan-cancer and PAAD. A significant correlation was observed between increased levels of ZP3 expression in PAAD patients and histologic grade (p = 0.026). Elevated ZP3 expression in PAAD was found to be significantly associated with poorer overall survival (p = 0.003), progression-free survival (p = 0.012), and disease-specific survival (p = 0.002). In PAAD, the level of ZP3 gene expression was statistically significant (p < 0.001) and recognized as a key determinant of patient prognosis. ZP3 exhibited associations with various biological pathways, including primary immunodeficiency, oxidative phosphorylation, and other pathways. ZP3 expression demonstrated correlations with immune infiltration, immune checkpoint genes, TMB, MSI, and mRNAsi in PAAD. Moreover, a pronounced negative correlation was detected between ZP3 expression levels and the therapeutic effectiveness of various medications, including selumetinib, bleomycin, FH535, docetaxel, and tanespimycin, within the context of PAAD. Elevated levels of ZP3 were consistently observed in cell line models of PAAD.

Conclusion: ZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients with PAAD.

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ZP3在胰腺腺癌中的表达及其对预后和治疗的意义。

背景：透明带糖蛋白3 （ZP3）在胰腺腺癌（PAAD）中的作用尚不清楚。目的：探讨ZP3在PAAD中的作用。方法：利用来自癌症基因组图谱（TCGA）的数据，对不同类型癌症和PAAD之间的ZP3基因表达进行比较分析，以了解差异。本研究旨在评估ZP3作为PAAD潜在诊断标志物的作用。仔细研究了ZP3水平与临床特征以及患者预后之间的关系。此外，基因组富集分析揭示了与ZP3相关的潜在调控机制。该研究进一步探讨了ZP3与免疫系统相互作用、检查点基因表达、肿瘤突变负荷（Tumor Mutational Burden， TMB）、微卫星不稳定性（microsatellite instability， MSI）和肿瘤干性指数（Tumor stemness index, mRNAsi）的关系。应用定量反转录PCR （qRT-PCR）技术证实了ZP3在PAAD细胞培养中的异常表达模式。结果：ZP3在泛癌和PAAD中均表现出异常表达。PAAD患者ZP3表达水平升高与组织学分级有显著相关性（p = 0.026）。发现PAAD中ZP3表达升高与较差的总生存期（p = 0.003）、无进展生存期（p = 0.012）和疾病特异性生存期（p = 0.002）显著相关。在PAAD中，ZP3基因表达水平有统计学意义（p < 0.001），被认为是患者预后的关键决定因素。ZP3与多种生物学途径相关，包括原发性免疫缺陷、氧化磷酸化和其他途径。在PAAD中，ZP3的表达与免疫浸润、免疫检查点基因、TMB、MSI和mRNAsi相关。此外，在PAAD的情况下，ZP3表达水平与各种药物的治疗效果呈显著负相关，包括selumetinib， bleomycin, FH535， docetaxel和tanespimycin。在PAAD细胞系模型中一致观察到ZP3水平升高。结论：ZP3具有作为PAAD患者预后生物标志物和治疗靶点的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis