He Lian, Xie Yusai, Qiu Yusong, Zhang Yong
Department of Pathology, Cancer Hospital of Dalian University of Technology (Liaoning Cancer Hospital & Institute), Shenyang, Liaoning, 110042, People's Republic of China.
Laboratory of Basic Medicine, General Hospital of Northern Theatre Command, Shenyang, Liaoning, 110016, People's Republic of China.
J Hepatocell Carcinoma. 2023 Aug 9;10:1309-1325. doi: 10.2147/JHC.S415224. eCollection 2023.
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.
ZPR1是一种含锌指蛋白，在神经退行性疾病、脂质代谢紊乱和非酒精性脂肪性肝病中起关键作用。然而，ZPR1在泛癌和肝细胞癌（HCC）中的表达模式、预后价值及治疗反应仍不清楚。
从UCSC Xena平台获取泛癌表达谱及相关临床数据。对ZPR1进行泛癌表达、表观遗传学特征及临床相关性分析。接下来，我们探讨了ZPR1在HCC中的预后意义及潜在生物学功能。此外，研究了ZPR1与免疫浸润及治疗反应之间的关系。最后，应用定量免疫组织化学（IHC）分析，使用Qupath软件评估ZPR1表达与HCC组织中免疫微环境的相关性。
ZPR1在大多数肿瘤类型中差异表达，在HCC中显著上调。ZPR1在大多数肿瘤中呈低甲基化状态。泛癌相关性分析表明，ZPR1与HCC的临床病理因素、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）及干性指数密切相关。ZPR1高表达可能是HCC不良预后的独立危险因素。ZPR1与免疫细胞浸润及治疗反应相关。最后，IHC结果表明，ZPR1与CD4、CD56、CD68和程序性死亡受体配体1（PD-L1）表达相关，是HCC中有前景的病理诊断标志物。
免疫浸润相关的ZPR1可被视为HCC治疗反应的新型负性预后生物标志物。
