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多组学分析揭示干扰素刺激基因 OAS1 可作为泛癌的预后和免疫生物标志物。

Multi-omics analysis reveals interferon-stimulated gene OAS1 as a prognostic and immunological biomarker in pan-cancer.

机构信息

Department of Hematology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

出版信息

Front Immunol. 2023 Oct 20;14:1249731. doi: 10.3389/fimmu.2023.1249731. eCollection 2023.

DOI:10.3389/fimmu.2023.1249731
PMID:37928544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10623006/
Abstract

INTRODUCTION

OAS1(2'-5'-oligoadenylate synthetase 1) is a member of the Interferon-Stimulated Genes which plays an important role in the antiviral process. In recent years, the role of OAS1 in tumors has attracted attention, and it was found to be associated with prognosis in several tumors. However, the mechanism by which OAS1 affects tumors is unclear and pan-cancer study of OAS1 is necessary to better understand its implication in cancers.

METHODS

The expression, prognostic value, genetic alteration, alternative splicing events of OAS1 in pan-cancers were analyzed using TCGA, GTEx, HPA, GEPIA and OncoSplicing databases. OAS1 associated immune cell infiltration was evaluated using the ESTIMATE, xCell, CIBERSORT and QUANTISEQ algorithm. Single cell transcriptome data download using TISH database. Finally, the roles of the OAS1 on apoptosis, migration and invasion were investigated in two pancreatic cancer cells.

RESULTS

Our results revealed significant differences in OAS1 expression among various tumors, which had prognostic implications. In addition, we investigated the impact of OAS1 on genomic stability, methylation status, and other factors across different types of cancer, and the effects of these factors on prognosis. Notably, our study also demonstrated that OAS1 overexpression can contribute to CTL dysfunction and macrophage M2 polarization. In addition, cell experiments showed that the knockdown of OAS1 could reduce the invasive ability and increased the apoptosis rate of PAAD cells.

DISCUSSION

These results confirmed that OAS1 could be a prognostic biomarker and therapeutic target for its potential role in CTL dysfunction and macrophage M2 polarization.

摘要

简介

OAS1(2'-5'-寡聚腺苷酸合成酶 1)是干扰素刺激基因的成员,在抗病毒过程中发挥重要作用。近年来,OAS1 在肿瘤中的作用引起了关注,并且在几种肿瘤中发现其与预后相关。然而,OAS1 影响肿瘤的机制尚不清楚,需要进行泛癌研究以更好地了解其在癌症中的意义。

方法

使用 TCGA、GTEx、HPA、GEPIA 和 OncoSplicing 数据库分析 OAS1 在泛癌中的表达、预后价值、遗传改变和可变剪接事件。使用 ESTIMATE、xCell、CIBERSORT 和 QUANTISEQ 算法评估 OAS1 相关免疫细胞浸润。使用 TISH 数据库下载单细胞转录组数据。最后,在两种胰腺癌细胞中研究了 OAS1 对细胞凋亡、迁移和侵袭的作用。

结果

我们的结果表明,OAS1 在各种肿瘤中的表达存在显著差异,这对预后有影响。此外,我们还研究了 OAS1 对不同类型癌症中基因组稳定性、甲基化状态和其他因素的影响,以及这些因素对预后的影响。值得注意的是,我们的研究还表明,OAS1 过表达可导致 CTL 功能障碍和巨噬细胞 M2 极化。此外,细胞实验表明,OAS1 的敲低可降低 PAAD 细胞的侵袭能力并增加细胞凋亡率。

讨论

这些结果证实,OAS1 可以作为一种预后生物标志物和治疗靶点,因为它在 CTL 功能障碍和巨噬细胞 M2 极化中具有潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/fc32c786923d/fimmu-14-1249731-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/2ce4fe26649e/fimmu-14-1249731-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/6abccd9bfdb8/fimmu-14-1249731-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/250f21f7c9b5/fimmu-14-1249731-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/56b1dd1afaef/fimmu-14-1249731-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/82e8ef86bde1/fimmu-14-1249731-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/96649eb54ec6/fimmu-14-1249731-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/fc32c786923d/fimmu-14-1249731-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/2ce4fe26649e/fimmu-14-1249731-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/6abccd9bfdb8/fimmu-14-1249731-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/cb552eb28ce5/fimmu-14-1249731-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/fa7b618b1a85/fimmu-14-1249731-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/250f21f7c9b5/fimmu-14-1249731-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/56b1dd1afaef/fimmu-14-1249731-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/82e8ef86bde1/fimmu-14-1249731-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/96649eb54ec6/fimmu-14-1249731-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6e1/10623006/fc32c786923d/fimmu-14-1249731-g009.jpg

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