Pregnancy Zone Protein Serves as a Prognostic Marker and Favors Immune Infiltration in Lung Adenocarcinoma.

Pregnancy Zone Protein Serves as a Prognostic Marker and Favors Immune Infiltration in Lung Adenocarcinoma.
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DOI:
10.3390/biomedicines11071978
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发表时间:
2023-07-13
期刊:
影响因子:
4.7
通讯作者:
--
中科院分区:
工程技术3区
文献类型:
--
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肺腺癌(LUAD)是一种发病率和死亡率都很高的公敌,目前尚无特异的生物标志物可供检测。妊娠区蛋白(PZP)是一种免疫相关蛋白,但其在LUAD中的作用尚不清楚。本研究利用生物信息学方法,结合免疫组织化学(IHC)、四色多重荧光免疫组织化学(MIHC)、实时定量聚合酶链式反应(qRT-PCR)和酶联免疫吸附试验(ELISA),探讨PZP在LUAD中的预后价值和潜在作用。结果表明,PZP在LUAD组织中的表达显著降低,与临床分期密切相关,可能是一个独立的预后不良因素。此外,通路分析表明,PZP在LUAD中的高表达主要涉及免疫相关分子。Ciberort免疫渗入分析显示,PZP的表达与多种免疫细胞的侵袭密切相关,免疫组化进一步证实PZP的表达与CD4+T细胞的侵袭呈正相关,与CD68+M0巨噬细胞的侵袭呈负相关。此外,mIHC还发现,PZP的表达导致CD86+M1巨噬细胞增多,CD206+M2巨噬细胞减少。因此,PZP可作为一种新的预测预后的生物标志物,有望成为治疗LUAD的免疫相关分子靶点。
Lung adenocarcinoma (LUAD) is a public enemy with a very high incidence and mortality rate, for which there is no specific detectable biomarker. Pregnancy zone protein (PZP) is an immune-related protein; however, the functions of PZP in LUAD are unclear. In this study, a series of bioinformatics methods, combined with immunohistochemistry (IHC), four-color multiplex fluorescence immunohistochemistry (mIHC), quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), were utilized to explore the prognostic value and potential role of PZP in LUAD. Our data revealed that PZP expression was markedly reduced in LUAD tissues, tightly correlated with clinical stage and could be an independent unfavorable prognostic factor. In addition, pathway analysis revealed that high expression of PZP in LUAD was mainly involved in immune-related molecules. Tumor immune infiltration analysis by CIBERSORT showed a significant correlation between PZP expression and several immune cell infiltrations, and IHC further confirmed a positive correlation with CD4+ T-cell infiltration and a negative correlation with CD68+ M0 macrophage infiltration. Furthermore, mIHC demonstrated that PZP expression gave rise to an increase in CD86+ M1 macrophages and a decrease in CD206+ M2 macrophages. Therefore, PZP can be used as a new biomarker for the prediction of prognosis and may be a promising immune-related molecular target for LUAD.
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