A comprehensive role evaluation and mechanism exploration of POGLUT2 in pan-cancer

Xianyun Xu; Guangming Xie; Mingfeng Xie; Qian Liu

doi:10.3389/fonc.2022.962540

A comprehensive role evaluation and mechanism exploration of POGLUT2 in pan-cancer

Front Oncol. 2022 Sep 8:12:962540. doi: 10.3389/fonc.2022.962540. eCollection 2022.

Authors

Xianyun Xu¹, Guangming Xie², Mingfeng Xie^{3

4}, Qian Liu^{4

5}

Affiliations

¹ Department of Clinical Laboratory, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China.
² School of Medicine, Tongji University, Shanghai, China.
³ Department of Pediatric Surgery, the First Affiliate Hospital of Gannan Medical University, Ganzhou, China.
⁴ Jiangxi Provincial Clinical Research Center for Vascular Anomalies, Gannan Medical University, Ganzhou, China.
⁵ Jiangxi Province Key Research Laboratory of Chinese Medicine for the Prevention and Treatment of Hemangioma, Jiangxi University of Chinese Medicine, Nanchang, China.

Abstract

Objective: To evaluate the role of POGLUT2 in pan-cancer through bioinformatics analysis and experimental verification.

Methods: Expression, gene mutation and amplification, methylation, and copy number alteration (CNA) of POGLUT2 were evaluated using The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) databases. Moreover, POGLUT2 on survival and disease progression in pan-cancer was performed using TCGA data. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuneScore, ImmuCellAI, and TIMER databases. POGLUT2 correlated drug resistance analysis was performed using the GDSC2 database. Furthermore, POGLUT2 knockdown of breast cancer cells was established, followed by in vitro biological function assays and in vivo tumor growth study. The mechanisms of POGLUT2 in breast cancer were briefly evaluated via its connection with Notch signaling.

Results: Increased levels of POGLUT2 were found in multiple types of cancer tissues and cell lines. Moreover, increased gene mutation and amplification, methylation, and CNA of POGLUT2 were found in several types of cancers. POGLUT2 was mainly expressed in stromal cells as verified by StromalScore, ESTIMATEScore, ImmuneScore, and Tumor purity, and POGLUT2 was positively correlated with cancer-associated fibroblasts, macrophages, monocytes, and neutrophils in the tumor microenvironment. In vitro and in vivo results showed that POGLUT2 knockdown could delay tumor growth and progression. Notch signaling components were related to the function of POGLUT2.

Conclusions: Increased levels of POGLUT2 could result in the dysregulated immune cell infiltration and tumor microenvironment and showed a significant regulatory effect on the progression of breast cancer through Notch-related signaling.

Keywords: POGLUT2; bioinformatic analysis; breast cancer; immune infiltration; pan cancer.