研究动态
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PRNP 是与结直肠癌 EMT 相关的泛癌预后和免疫相关性。

PRNP is a pan-cancer prognostic and immunity-related to EMT in colorectal cancer.

发表日期:2024
作者: Haifeng Chen, Yao Du, Zhiyuan Kong, Xinghe Liao, Weiping Li
来源: Frontiers in Cell and Developmental Biology

摘要:

朊病毒蛋白基因(PRNP)广泛表达于多种组织中。尽管已经研究了 PRNP 在多种癌症中的作用,但还没有泛癌分析揭示其与肿瘤发生和免疫的关系。对来自加州大学圣克鲁斯分校的癌症基因组图谱 (TCGA) 泛癌数据集进行了综合分析( UCSC)数据库来确定 PRNP 的表达及其潜在的预后影响。使用免疫浸润和富集分析方法来确定 PRNP 表达水平、肿瘤免疫和免疫治疗之间的相关性。此外,还采用基因本体论(GO)和京都基因和基因组百科全书(KEGG)方法来检查涉及 PRNP 的可能信号通路。体外实验采用CCK-8实验、伤口愈合实验和Transwell实验检测细胞朊病毒蛋白(PrPC)对结直肠癌(CRC)细胞增殖、迁移和侵袭的影响。通过蛋白质印迹法检测上皮间质转化(EMT)相关蛋白(N-钙粘蛋白、E-钙粘蛋白、波形蛋白和Snail)的表达水平。在大多数癌症类型中,PRNP高水平表达,这与患者的预后。 PRNP 表达与免疫浸润细胞、免疫抑制细胞浸润和免疫检查点分子密切相关。除了肿瘤突变负荷 (TMB) 之外,在几种癌症中还检测到 PRNP 表达与微卫星不稳定性 (MSI) 之间存在显着相关性。体外细胞研究推断,PrPC 增强 CRC 细胞的增殖、迁移、侵袭和 EMT。PRNP 作为免疫相关的预后标志物,有望预测 CRC 免疫治疗相关的结果,同时促进细胞增殖、迁移和侵袭活动。此外,它还可能在 CRC 内部管理 EMT 监管方面发挥作用。版权所有 © 2024 Chen、Du、Kong、Liao 和 Li。
Prion protein gene (PRNP) is widely expressed in a variety of tissues. Although the roles of PRNP in several cancers have been investigated, no pan-cancer analysis has revealed its relationship with tumorigenesis and immunity.Comprehensive analyses were conducted on The Cancer Genome Atlas (TCGA) Pan-Cancer dataset from the University of California Santa Cruz (UCSC) database to determine the expression of PRNP and its potential prognostic implications. Immune infiltration and enrichment analysis methods were used to ascertain correlations between PRNP expression levels, tumor immunity, and immunotherapy. Additionally, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods were employed to examine possible signaling pathways involving PRNP. In vitro experiments using CCK-8 assay, Wound healing assay, and Transwell assay to detect the effect of Cellular prion protein (PrPC) on proliferation, migration, and invasion in colorectal cancer (CRC) cells. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins (N-cadherin, E-cadherin, Vimentin and Snail) were detected by western blot.Among most cancer types, PRNP is expressed at high levels, which is linked to the prognosis of patients. PRNP expression is strongly associated with immune infiltrating cells, immunosuppressive cell infiltration and immune checkpoint molecules. In addition to tumor mutation burden (TMB), substantial correlations are detected between PRNP expression and microsatellite instability (MSI) in several cancers. In vitro cell studies inferred that PrPC enhanced the proliferation, migration, invasion, and EMT of CRC cells.PRNP serves as an immune-related prognostic marker that holds promise for predicting outcomes related to CRC immunotherapy while simultaneously promoting cell proliferation, migration, and invasion activities. Furthermore, it potentially plays a role in governing EMT regulation within CRC.Copyright © 2024 Chen, Du, Kong, Liao and Li.