Prognostic value and immune-infiltration pattern of FOXD3-AS1 in patients with glioma

Zhenhua Chen; Yi Zhang; Sujuan Feng; Jiaqi Yuan; Dongliang Shi; Yong Wang; Yongdong Li; Jun Dong

doi:10.3389/fphar.2023.1162309

Prognostic value and immune-infiltration pattern of FOXD3-AS1 in patients with glioma

Front Pharmacol. 2023 Apr 4:14:1162309. doi: 10.3389/fphar.2023.1162309. eCollection 2023.

Authors

Zhenhua Chen^{1

2}, Yi Zhang², Sujuan Feng³, Jiaqi Yuan¹, Dongliang Shi⁴, Yong Wang², Yongdong Li¹, Jun Dong¹

Affiliations

¹ Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Neurosurgery, Affiliated Hospital 2 of Nantong University and Affiliated Hospital of Kangda College of Nanjing Medical University, Nantong, China.
³ Department of Nephrology, Affiliated Hospital 2 of Nantong University and Affiliated Hospital of Kangda College of Nanjing Medical University, Nantong, China.
⁴ Department of Neurosurgery, Joint Logistics Support Unit No 904 Hospital, Wuxi, China.

Abstract

Gliomas are difficult-to-treat brain tumors due to their aggressive nature, rapid proliferation, and high invasiveness (Zhang et al., J Cell Biochem, 2019, 120 (9), 15106-15118; Ge et al., Int J Biochem Cell Biol, 2021, 139, 106054). FOXD3-AS1 has been identified as an emerging potential target for tumor prediction and treatment in many studies (Qin et al., Front Oncol, 2021, 11, 688027). However, the utility of FOXD3-AS1 has not been reported in glioma patients (Li et al., Cancer Manag Res, 2021, 13, 9037-9048). The differential profiles of FOXD3-AS1 in TCGA-GBMLGG database were analyzed across clinical subgroups. The analysis of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) revealed that a high level of FOXD3-AS1 was associated with a poor prognosis and survival outcome. Based on the Cox regression analysis, FOXD3-AS1 was found to be a high-risk factor for glioma that affects prognosis outcomes independently. More importantly, because oxidative stress is closely linked to glioma prognosis, we focused on the potential mechanisms of six oxidative stress co-expressed genes with FOXD3-AS1. In addition, the predictive value of FOXD3-AS1 was determined for each clinical subgroup status. The ROC curve results showed that FOXD3-AS1 had a good predictive performance. A stratified clinicopathological subgroup analysis revealed that high expression of FOXD3-AS1 is associated with a poor prognosis. This also indicates a link between FOXD3-AS1 and tumorigenesis and prognosis, which has potential application value. Furthermore, the immune cell infiltration of FOXD3-AS1 and the signal marker correlation suggested that immune cell infiltration differed significantly between immune cell subsets. To the best of our knowledge, this is the first report to investigate FOXD3-AS1 in glioma and how it may modulate GBM and LGG immune microenvironments. Furthermore, FOXD3-AS1 was detected in tumor and paraneoplastic tissues using RT-qPCR. Transwell analysis verified the migration and invasion of the FOXD3-AS1 knockout group in vitro to a certain extent. In conclusion, FOXD3-AS1 can be used as a prognostic indicator for GBM and LGG, and it is closely related to immune infiltration and response to oxidative stress, which may contribute to the advancement of glioma immunotherapy research.

Keywords: FOXD3-AS1; TCGA; immune infiltration; oxidative stress; prognosis.

Grants and funding

Jiangsu Province Key Research and Development Program: Social Development Project (BE2021653); Key Project of Jiangsu Health Commission (ZDB2020016); Natural Science Foundation of Jiangsu Province (BK20201172); Science and Technology Support Program of Nantong (JC2021179, MS12021041); Science Foundation of Nantong First People’s Hospital (YPYJJZD006); Science Foundation of Kangda College of Nanjing Medical University (KD2022KYJJZD023).