全癌症分析和数字病理学研究揭示了与肝细胞癌免疫浸润和治疗反应相关的负预后生物标志物ZPR1。
Pan-Cancer Profiling and Digital Pathology Analysis Reveal Negative Prognostic Biomarker ZPR1 Associated with Immune Infiltration and Treatment Response in Hepatocellular Carcinoma.
发表日期:2023
作者:
Lian He, Yusai Xie, Yusong Qiu, Yong Zhang
来源:
Epigenetics & Chromatin
摘要:
ZPR1是一种含锌指结构的蛋白质,在神经变性疾病、脂质代谢紊乱和非酒精性脂肪性肝病中扮演关键角色。然而,关于ZPR1在全癌和肝细胞瘤(HCC)中的表达模式、预后价值和治疗反应仍不清楚。我们从UCSC Xena平台获取了全癌表达谱和相关临床数据。对ZPR1进行了全癌表达、表观遗传学分析和临床相关性分析。我们接下来探讨了ZPR1在HCC中的预后意义和潜在生物学功能。此外,还研究了ZPR1与免疫浸润和治疗反应的关系。最后,应用定量免疫组织化学(IHC)分析和Qupath软件评估ZPR1的表达与HCC组织中的免疫微环境的相关性。ZPR1在大多数肿瘤类型中表达差异显著,且在HCC中显著上调。ZPR1在大多数肿瘤中呈低甲基化状态。全癌相关性分析表明,ZPR1与HCC中的临床病理因素、TMB、MSI和干细胞指数密切相关。高表达的ZPR1可能是HCC不良预后的独立危险因素。ZPR1与免疫细胞浸润和治疗反应相关。最后,IHC结果表明ZPR1与CD4、CD56、CD68和PD-L1的表达相关,是HCC中有潜在病理诊断价值的标志物。与免疫浸润相关的ZPR1可以被视为HCC治疗反应的新的负预后生物标志物。© 2023 He等。
ZPR1 is a zinc finger-containing protein that plays a crucial role in neurodegenerative diseases, lipid metabolism disorders, and non-alcoholic fatty liver disease. However, the expression pattern, prognostic value, and treatment response of ZPR1 in pan-cancer and hepatocellular carcinoma (HCC) remain unclear.Pan-cancer expression profiles and relevant clinical data were acquired from UCSC Xena platform. Pan-cancer expression, epigenetic profile, and clinical correlation analysis for ZPR1 were performed. We next explored the prognostic significance and potential biological functions of ZPR1 in HCC. Furthermore, the relationship between ZPR1 and immune infiltration and treatment response was investigated. Finally, quantitative immunohistochemistry (IHC) analysis was applied to assess the correlation of ZPR1 expression and immune microenvironment in HCC tissues using Qupath software.ZPR1 was differentially expressed in most tumor types and significantly up-regulated in HCC. ZPR1 showed hypo-methylated status in most tumors. Pan-cancer correlation analysis indicated that ZPR1 was closely associated with clinicopathological factors and TMB, MSI, and stemness index in HCC. High ZPR1 expression could be an independent risk factor for adverse prognosis in HCC. ZPR1 correlated with immune cell infiltration and therapeutic response. Finally, IHC results suggested that ZPR1 correlated with CD4, CD56, CD68, and PD-L1 expression and is a promising pathological diagnostic marker in HCC.Immune infiltrate-associated ZPR1 could be considered a novel negative prognostic biomarker for therapeutic response in HCC.© 2023 He et al.