Comprehensive Analysis About Prognostic and Immunological Role of WTAP in Pan-cancer

Overview

Journal Front Genet

Date 2022 Sep 29

PMID 36171885

Authors

Jiangchu Lei

Yuzhi Fan

Chaobiao Yan

Yeernaer Jiamaliding

Yang Tang

Jiawei Zhou

Mengna Huang

Guomin Ju

Jian Wu

Chuanhui Peng

Affiliations

Soon will be listed here.

Abstract

Wilms tumor 1-associated protein (WTAP) plays a critical role in ribonucleic acid (RNA) methylation of N6 adenosine (mA) modification, which is closely related with varieties of biological process. However, the role of WTAP in cancers remains to be determined. This study is designed to demonstrate the prognostic landscape of WTAP in pan-cancer and explore the relationship between WTAP expression and immune infiltration. Here, we investigated the expression level and prognostic role of WTAP in pan-cancer using multiple databases, including PrognoScan, GEPIA, and Kaplan-Meier Plotter. Then, applying the GEPIA and TIMER databases, we illustrated the correlations between WTAP expression and immune infiltration in tumors, especially liver hepatocellular carcinoma (LIHC), and esophageal carcinoma (ESCA). WTAP had significant higher expression levels in tumor tissues of ESCA, LIHC, etc., while lower expression levels in those of bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), etc. And WTAP demonstrated multifaceted prognostic value in cancers. Of our interests, WTAP exerted a harmful effect on LIHC patient for overall survival (OS) and progression free survival (PFS). WTAP expression also significantly associated with the infiltration levels of B cells, CD8 T cells, CD4 T cells, macrophages, neutrophils, and dendritic cells (DC) in LIHC but not ESCA. Furthermore, combined analysis about WTAP expression level and immune cell specific gene markers implied WTAP correlates with regulatory cells (T reg) infiltration in LIHC and ESCA. The mA regulator WTAP can serve as a prognostic biomarker for certain tumor types in pan-cancer and potentially result from immune cell infiltration.

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References

Horiuchi K, Umetani M, Minami T, Okayama H, Takada S, Yamamoto M . Wilms' tumor 1-associating protein regulates G2/M transition through stabilization of cyclin A2 mRNA. Proc Natl Acad Sci U S A. 2006; 103(46):17278-83. PMC: 1634838. DOI: 10.1073/pnas.0608357103. View

Mizuno H, Kitada K, Nakai K, Sarai A . PrognoScan: a new database for meta-analysis of the prognostic value of genes. BMC Med Genomics. 2009; 2:18. PMC: 2689870. DOI: 10.1186/1755-8794-2-18. View

Wang C, Tang C, Wang Y, Huang B, Hu G, Wang Q . Upregulated WTAP expression appears to both promote breast cancer growth and inhibit lymph node metastasis. Sci Rep. 2022; 12(1):1023. PMC: 8770795. DOI: 10.1038/s41598-022-05035-y. View

Jiang X, Liu B, Nie Z, Duan L, Xiong Q, Jin Z . The role of m6A modification in the biological functions and diseases. Signal Transduct Target Ther. 2021; 6(1):74. PMC: 7897327. DOI: 10.1038/s41392-020-00450-x. View

Nagy A, Lanczky A, Menyhart O, Gyorffy B . Validation of miRNA prognostic power in hepatocellular carcinoma using expression data of independent datasets. Sci Rep. 2018; 8(1):9227. PMC: 6003936. DOI: 10.1038/s41598-018-27521-y. View

Li Z, Zheng Z, Yang P, Lin L, Zhou G, Lv J . WTAP-mediated mA modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis. Cell Death Differ. 2022; 29(6):1137-1151. PMC: 9177844. DOI: 10.1038/s41418-021-00905-w. View

Duan H, Wang Y, Jia G . Dynamic and reversible RNA N -methyladenosine methylation. Wiley Interdiscip Rev RNA. 2018; 10(1):e1507. DOI: 10.1002/wrna.1507. View

Zhu X, Zhang J, Zhuang P, Zhu H, Zhang W, Xiong Y . High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol. 2008; 26(16):2707-16. DOI: 10.1200/JCO.2007.15.6521. View

Gu C, Shi X, Qiu W, Huang Z, Yu Y, Shen F . Comprehensive Analysis of the Prognostic Role and Mutational Characteristics of m6A-Related Genes in Lung Squamous Cell Carcinoma. Front Cell Dev Biol. 2021; 9:661792. PMC: 8027321. DOI: 10.3389/fcell.2021.661792. View

10.

Tang J, Wang F, Cheng G, Si S, Sun X, Han J . Wilms' tumor 1-associating protein promotes renal cell carcinoma proliferation by regulating CDK2 mRNA stability. J Exp Clin Cancer Res. 2018; 37(1):40. PMC: 5827993. DOI: 10.1186/s13046-018-0706-6. View

11.

Cheng N, Bai X, Shu Y, Ahmad O, Shen P . Targeting tumor-associated macrophages as an antitumor strategy. Biochem Pharmacol. 2020; 183:114354. DOI: 10.1016/j.bcp.2020.114354. View

12.

Dai D, Wang H, Zhu L, Jin H, Wang X . N6-methyladenosine links RNA metabolism to cancer progression. Cell Death Dis. 2018; 9(2):124. PMC: 5833385. DOI: 10.1038/s41419-017-0129-x. View

13.

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

14.

Gao Y, Zhou H, Liu G, Wu J, Yuan Y, Shang A . Tumor Microenvironment: Lactic Acid Promotes Tumor Development. J Immunol Res. 2022; 2022:3119375. PMC: 9207018. DOI: 10.1155/2022/3119375. View

15.

Topalian S, Drake C, Pardoll D . Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015; 27(4):450-61. PMC: 4400238. DOI: 10.1016/j.ccell.2015.03.001. View

16.

Hong M, Clubb J, Chen Y . Engineering CAR-T Cells for Next-Generation Cancer Therapy. Cancer Cell. 2020; 38(4):473-488. DOI: 10.1016/j.ccell.2020.07.005. View

17.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

18.

Li B, Liang Z, Seery S, Liu Q, You L, Zhang T . WT1 associated protein promotes metastasis and chemo-resistance to gemcitabine by stabilizing Fak mRNA in pancreatic cancer. Cancer Lett. 2019; 451:48-57. DOI: 10.1016/j.canlet.2019.02.043. View

19.

Li M, Zha X, Wang S . The role of N6-methyladenosine mRNA in the tumor microenvironment. Biochim Biophys Acta Rev Cancer. 2021; 1875(2):188522. DOI: 10.1016/j.bbcan.2021.188522. View

20.

Chen L, Wang X . Relationship between the genetic expression of WTAP and bladder cancer and patient prognosis. Oncol Lett. 2018; 16(6):6966-6970. PMC: 6256415. DOI: 10.3892/ol.2018.9554. View