Lyu Guizhen, Li Dongbing
Scientific Research Center, Dongguan Labway Medical Testing Laboratory Co., Ltd., Dongguan, 523429, China.
Scientific Research Center, Beijing ChosenMed Clinical Laboratory Co., Ltd. Beijing, 100176, China.
Protein Pept Lett. 2025;32(2):124-138. doi: 10.2174/0109298665350171241204153202.
The role of Zona pellucida glycoprotein 3 (ZP3) is unclear in pancreatic adenocarcinoma (PAAD).
This study aimed to explore the role of ZP3 in PAAD.
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.
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.
ZP3 has the potential to serve as a prognostic biomarker and therapeutic target for patients with PAAD.
透明带糖蛋白3（ZP3）在胰腺腺癌（PAAD）中的作用尚不清楚。
本研究旨在探讨ZP3在PAAD中的作用。
利用来自癌症基因组图谱（TCGA）的数据，对ZP3基因表达进行比较分析，以辨别各种类型癌症与PAAD之间的差异。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，进行了基因组富集分析，以揭示与ZP3相关的潜在调控机制。该研究进一步深入探讨了ZP3与免疫系统相互作用、检查点基因表达、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）和肿瘤干性指数（mRNAsi）之间的关联。通过应用定量逆转录PCR（qRT-PCR）技术，证实了PAAD细胞培养物中ZP3的异常表达模式。
ZP3在泛癌和PAAD中均表现出异常表达。在PAAD患者中，ZP3表达水平升高与组织学分级之间存在显著相关性（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基因表达水平具有统计学意义（p < 0.001），并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的背景下，检测到ZP3表达水平与包括司美替尼、博来霉素、FH535、多西他赛和坦西莫司在内的各种药物的治疗效果之间存在显著负相关。在PAAD的细胞系模型中持续观察到ZP3水平升高。
ZP3有可能作为PAAD患者的预后生物标志物和治疗靶点。
