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犬乳腺肿瘤中 PD-L1mRNA 和蛋白的表达:与组织病理学分级和分子标志物的相关性。

PD-L1 mRNA and protein expression in canine mammary carcinomas: Correlation with histopathological grade and molecular markers.

机构信息

Konkuk University, Seoul, Korea.

University of Illinois Urbana-Champaign, Urbana, IL.

出版信息

Vet Pathol. 2024 May;61(3):402-409. doi: 10.1177/03009858241226621. Epub 2024 Jan 28.

DOI:10.1177/03009858241226621
PMID:38281145
Abstract

Programmed death ligand 1 (PD-L1) is an immune checkpoint molecule that plays a crucial role in regulating antitumor immune responses. Canine mammary carcinomas (CMCs) are common tumors of dogs. Despite extensive studies on the heterogeneity of CMCs, there is still a lack of effective precision therapies for the treatment of CMCs. In this study, we aimed to investigate the correlation between PD-L1 mRNA and protein expression in CMCs and explore its association with histopathological grade and molecular markers, including the estrogen receptor, epidermal growth factor receptor 2, and cytokeratin 5/6 (CK5/6). Formalin-fixed paraffin-embedded samples were evaluated for mRNA expression using RNA hybridization and PD-L1 protein expression using immunohistochemistry. We observed no substantial correlation between PD-L1 mRNA and protein expression in CMCs; however, mRNA levels were significantly higher in grade 3 than in grade 1 tumors ( = .001). In addition, we observed a positive correlation between PD-L1 protein expression and CK5/6 expression in CMCs ( = .032). These findings suggest that PD-L1 expression in CMCs is heterogeneous and may be regulated post-transcriptionally. Further studies are needed to explore the prognostic and therapeutic implications of PD-L1 expression in different molecular subtypes of CMCs and their potential as predictive biomarkers for immunotherapy.

摘要

程序性死亡配体 1(PD-L1)是一种免疫检查点分子,在调节抗肿瘤免疫反应中起着关键作用。犬乳腺肿瘤(CMCs)是犬的常见肿瘤。尽管对 CMCs 的异质性进行了广泛的研究,但仍然缺乏有效的精准治疗方法来治疗 CMCs。在这项研究中,我们旨在研究 CMCs 中 PD-L1mRNA 和蛋白表达之间的相关性,并探讨其与组织病理学分级和分子标志物(包括雌激素受体、表皮生长因子受体 2 和细胞角蛋白 5/6(CK5/6))的关联。使用 RNA 杂交评估福尔马林固定石蜡包埋样本中的 mRNA 表达,并用免疫组织化学评估 PD-L1 蛋白表达。我们观察到 CMCs 中 PD-L1mRNA 和蛋白表达之间没有实质性相关性;然而,3 级肿瘤的 mRNA 水平明显高于 1 级肿瘤(=.001)。此外,我们观察到 CMCs 中 PD-L1 蛋白表达与 CK5/6 表达之间存在正相关(=.032)。这些发现表明 CMCs 中 PD-L1 表达具有异质性,并且可能是转录后调节的。需要进一步研究来探讨 CMCs 不同分子亚型中 PD-L1 表达的预后和治疗意义及其作为免疫治疗预测生物标志物的潜力。

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