Comprehensive analysis about prognostic and immunological role of WTAP in pan-cancer

Abstract

Background: Wilms tumor 1-associated protein (WTAP) plays a critical role in ribonucleic acid (RNA) methylation of N6 adenosine (m6A) 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.Methods: 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).Results: 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.Conclusion: The m6A regulator WTAP can serve as a prognostic biomarker for certain tumor types in pan-cancer and potentially result from immune cell infiltration.

RNA m6A methylation regulators in liver cancer

“…We can often see WTAP disordered in cancer with cancer specific pattern. For example, WTAP is up-regulated in stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC) and hepatocellular carcinoma (HCC), while down-regulated in uterine corpus endometrial carcinoma (UCEC), thyroid cancer (THCA), lung adenocarcinoma (LUAD), and bladder urothelial carcinoma (BLCA) [ 72 , 80 ]. WTAP is also an oncogene associated with heat shock protein 90 in AML and diffuse large B-cell lymphoma [ 81 ].…”

“…However, Wilms tumor 1 associated protein (WTAP), an important component of m6A methylation, is understudied in HCC. Research shows that the expression levels of WTAP in liver cancer tissues are significantly higher than that in the adjacent normal tissues, which is significantly connected with the clinical stage in patients with HCC [ 79 , 80 , 82 , 83 ]. The high expression of WTAP in HCC also reveals poor prognosis and patient survival [ 84 ].…”

The current landscape of m6A modification in urological cancers

“…It was reported that the expression levels of HNRNPC and YTHDF1 increased, while the expression levels of Vir-like m6A methyltransferase associated (VIRMA/KIAA1429), zinc finger CCCH-type containing 13 (ZC3H13), METTL14, ALKBH5, and YTHDF2 decreased in pRCC tissues ( Yang et al, 2021b ). Lei et al (2022) revealed that the transcription level of WTAP reduced in pRCC and chRCC. Different m6A RNA methylation regulators also make different contributions to RCC.…”