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PRNP是一种与结直肠癌的全癌预后及上皮-间质转化相关的免疫蛋白。

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

作者信息

Chen Haifeng, Du Yao, Kong Zhiyuan, Liao Xinghe, Li Weiping

机构信息

Department of Gastroenterology, The First People's Hospital of Taicang City, Taicang Affiliated Hospital of Soochow University, Taicang, Jiangsu, China.

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Front Cell Dev Biol. 2024 Aug 5;12:1391873. doi: 10.3389/fcell.2024.1391873. eCollection 2024.

DOI:10.3389/fcell.2024.1391873
PMID:39170916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11336278/
Abstract

BACKGROUND

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.

METHODS

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. 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.

RESULTS

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. cell studies inferred that PrPC enhanced the proliferation, migration, invasion, and EMT of CRC cells.

CONCLUSION

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.

摘要

背景

朊病毒蛋白基因（PRNP）在多种组织中广泛表达。尽管已经研究了PRNP在几种癌症中的作用，但尚无泛癌分析揭示其与肿瘤发生和免疫的关系。

方法

对来自加利福尼亚大学圣克鲁兹分校（UCSC）数据库的癌症基因组图谱（TCGA）泛癌数据集进行综合分析，以确定PRNP的表达及其潜在的预后意义。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，采用基因本体论（GO）和京都基因与基因组百科全书（KEGG）方法来研究涉及PRNP的可能信号通路。使用CCK-8测定、伤口愈合测定和Transwell测定来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。通过蛋白质免疫印迹法检测上皮-间质转化（EMT）相关蛋白（N-钙黏蛋白、E-钙黏蛋白、波形蛋白和蜗牛蛋白）的表达水平。

结果

在大多数癌症类型中，PRNP高水平表达，这与患者的预后相关。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。除肿瘤突变负荷（TMB）外，在几种癌症中还检测到PRNP表达与微卫星不稳定性（MSI）之间存在显著相关性。细胞研究推断，PrPC增强了CRC细胞的增殖、迁移、侵袭和EMT。

结论

PRNP作为一种免疫相关的预后标志物，有望预测与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，它可能在CRC的EMT调节中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e2e/11336278/20b3189c7e0b/fcell-12-1391873-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e2e/11336278/d3f080650a91/fcell-12-1391873-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e2e/11336278/60b6c6c1ab01/fcell-12-1391873-g009.jpg
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