多组学分析揭示干扰素刺激基因 OAS1 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.
发表日期:2023
作者:
Runyu Yang, Yue Du, Mengyao Zhang, Yi Liu, Hui Feng, Ruimin Liu, Bingyu Yang, Jiayi Xiao, Pengcheng He, Fan Niu
来源:
Frontiers in Immunology
摘要:
OAS1(2'-5'-寡腺苷酸合成酶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人们的关注,并发现它与多种肿瘤的预后相关。然而,OAS1影响肿瘤的机制尚不清楚,有必要对OAS1进行泛癌研究,以更好地了解其在癌症中的意义。利用TCGA分析OAS1在泛癌中的表达、预后价值、遗传改变、选择性剪接事件、GTEx、HPA、GEPIA 和 OncoSplicing 数据库。使用 ESTIMATE、xCell、CIBERSORT 和 QUANTISEQ 算法评估 OAS1 相关的免疫细胞浸润。使用 TISH 数据库下载单细胞转录组数据。最后,我们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。我们的结果揭示了各种肿瘤中 OAS1 表达的显着差异,这具有预后意义。此外,我们还研究了 OAS1 对不同类型癌症的基因组稳定性、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 过度表达可能导致 CTL 功能障碍和巨噬细胞 M2 极化。此外,细胞实验表明,OAS1的敲低可以降低PAAD细胞的侵袭能力并增加其凋亡率。这些结果证实OAS1因其在CTL功能障碍和巨噬细胞M2极化中的潜在作用而可以成为预后生物标志物和治疗靶点。版权所有 © 2023 杨、杜、张、刘、冯、刘、杨、肖、何、牛。
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.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.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.These results confirmed that OAS1 could be a prognostic biomarker and therapeutic target for its potential role in CTL dysfunction and macrophage M2 polarization.Copyright © 2023 Yang, Du, Zhang, Liu, Feng, Liu, Yang, Xiao, He and Niu.