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

被引:10
作者
Yang, Runyu [1 ]
Du, Yue [1 ]
Zhang, Mengyao [1 ]
Liu, Yi [1 ]
Feng, Hui [1 ]
Liu, Ruimin [1 ]
Yang, Bingyu [1 ]
Xiao, Jiayi [1 ]
He, Pengcheng [1 ]
Niu, Fan [1 ]
机构
[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Hematol, Xian, Shaanxi, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
OAS1; tumor immune microenvironment; immunotherapeutic resistance; T-cell dysfunction; pan-cancer; IMMUNE-RESPONSES; EXPRESSION; RNA; MACROPHAGES; PROGRESSION; RESISTANCE; BLOCKADE; INSIGHTS; CELLS;
D O I
10.3389/fimmu.2023.1249731
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IntroductionOAS1(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.MethodsThe 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.ResultsOur 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.DiscussionThese results confirmed that OAS1 could be a prognostic biomarker and therapeutic target for its potential role in CTL dysfunction and macrophage M2 polarization.
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页数:19
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共 83 条
[1]   Type I interferon signaling and macrophages: a double-edged sword? [J].
Adler, Barbara ;
Adler, Heiko .
CELLULAR & MOLECULAR IMMUNOLOGY, 2022, 19 (09) :967-968
[2]   The status of tumor mutational burden and immunotherapy [J].
Anagnostou, Valsamo ;
Bardelli, Alberto ;
Chan, Timothy A. ;
Turajlic, Samra .
NATURE CANCER, 2022, 3 (06) :652-656
[3]   xCell: digitally portraying the tissue cellular heterogeneity landscape [J].
Aran, Dvir ;
Hu, Zicheng ;
Butte, Atul J. .
GENOME BIOLOGY, 2017, 18
[4]   Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1 [J].
Baris, Safa ;
Alroqi, Fayhan ;
Kiykim, Ayca ;
Karakoc-Aydiner, Elif ;
Ogulur, Ismail ;
Ozen, Ahmet ;
Charbonnier, Louis-Marie ;
Bakir, Mustafa ;
Boztug, Kaan ;
Chatila, Talal A. ;
Barlan, Isil B. .
JOURNAL OF CLINICAL IMMUNOLOGY, 2016, 36 (07) :641-648
[5]   Opposing Functions of Interferon Coordinate Adaptive and Innate Immune Responses to Cancer Immune Checkpoint Blockade [J].
Benci, Joseph L. ;
Johnson, Lexus R. ;
Choa, Ruth ;
Xu, Yuanming ;
Qiu, Jingya ;
Zhou, Zilu ;
Xu, Bihui ;
Ye, Darwin ;
Nathanson, Katherine L. ;
June, Carl H. ;
Wherry, E. John ;
Zhang, Nancy R. ;
Ishwaran, Hemant ;
Hellmann, Matthew D. ;
Wolchok, Jedd D. ;
Kambayashi, Taku ;
Minn, Andy J. .
CELL, 2019, 178 (04) :933-+
[6]   Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade [J].
Benci, Joseph L. ;
Xu, Bihui ;
Qiu, Yu ;
Wu, Tony J. ;
Dada, Hannah ;
Twyman-Saint Victor, Christina ;
Cucolo, Lisa ;
Lee, David S. M. ;
Pauken, Kristen E. ;
Huang, Alexander C. ;
Gangadhar, Tara C. ;
Amaravadi, Ravi K. ;
Schuchter, Lynn M. ;
Feldman, Michael D. ;
Ishwaran, Hemant ;
Vonderheide, Robert H. ;
Maity, Amit ;
Wherry, E. John ;
Minn, Andy J. .
CELL, 2016, 167 (06) :1540-+
[7]   Understanding the tumor immune microenvironment (TIME) for effective therapy [J].
Binnewies, Mikhail ;
Roberts, Edward W. ;
Kersten, Kelly ;
Chan, Vincent ;
Fearon, Douglas F. ;
Merad, Miriam ;
Coussens, Lisa M. ;
Gabrilovich, Dmitry I. ;
Ostrand-Rosenberg, Suzanne ;
Hedrick, Catherine C. ;
Vonderheide, Robert H. ;
Pittet, Mikael J. ;
Jain, Rakesh K. ;
Zou, Weiping ;
Howcroft, T. Kevin ;
Woodhouse, Elisa C. ;
Weinberg, Robert A. ;
Krummel, Matthew F. .
NATURE MEDICINE, 2018, 24 (05) :541-550
[8]   Landscape of Microsatellite Instability Across 39 Cancer Types [J].
Bonneville, Russell ;
Krook, Melanie A. ;
Kautto, Esko A. ;
Miya, Jharna ;
Wing, Michele R. ;
Chen, Hui-Zi ;
Reeser, Julie W. ;
Yu, Lianbo ;
Roychowdhury, Sameek .
JCO PRECISION ONCOLOGY, 2017, 1 :1-15
[9]   The ever-increasing importance of cancer as a leading cause of premature death worldwide [J].
Bray, Freddie ;
Laversanne, Mathieu ;
Weiderpass, Elisabete ;
Soerjomataram, Isabelle .
CANCER, 2021, 127 (16) :3029-3030
[10]   Interleukins in cancer: from biology to therapy [J].
Briukhovetska, Dania ;
Dorr, Janina ;
Endres, Stefan ;
Libby, Peter ;
Dinarello, Charles A. ;
Kobold, Sebastian .
NATURE REVIEWS CANCER, 2021, 21 (08) :481-499