Noncoding RNA-Mediated High Expression of PFKFB3 Correlates with Poor Prognosis and Tumor Immune Infiltration of Lung Adenocarcinoma

Xue Gu; Xiaoli Li; Xue Zhang; Li Tong; Ran Feng; Lei Liu; Hui Sun; Qing Zhang; Tingting Bian; Jianguo Zhang; Lihua Gao; Chenxi Zhang; Jian Liu; Yifei Liu

doi:10.2147/OTT.S416155

Noncoding RNA-Mediated High Expression of PFKFB3 Correlates with Poor Prognosis and Tumor Immune Infiltration of Lung Adenocarcinoma

Onco Targets Ther. 2023 Sep 22:16:767-783. doi: 10.2147/OTT.S416155. eCollection 2023.

Authors

Xue Gu^#¹, Xiaoli Li^#¹, Xue Zhang^#², Li Tong³, Ran Feng¹, Lei Liu¹, Hui Sun¹, Qing Zhang¹, Tingting Bian¹, Jianguo Zhang¹, Lihua Gao², Chenxi Zhang⁴, Jian Liu², Yifei Liu¹

Affiliations

¹ Department of Pathology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, People's Republic of China.
² Department of Oncology, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, 226001, People's Republic of China.
³ Department of Pathology, Affiliated Hospital of Nantong University, Dalian Medical University, Nantong, 226001, People's Republic of China.
⁴ Medical School of Nantong University, Nantong, 226001, People's Republic of China.

^# Contributed equally.

Abstract

Background: There is growing evidence showing that 6-phosphofructo-2-kinase (PFKFB3) plays crucial roles in different types of human cancers, including LUAD; however, the specific mechanism by which PFKFB3 plays a role in LUAD remains unclear.

Methods: We investigated the expression of PFKFB3 and explored the underlying mechanism as well as the correlation with immune markers using several online datasets, such as Tumor Immune Estimate Resource (TIMER), UALCAN, and the Cancer Genome Atlas (TCGA) databases, miRWalk, Targetscan, MiRDB and starBase database. Western blot and immunohistochemistry analysis were performed to verify the corresponding outcomes.

Results: It was shown that the mRNA expression of PFKFB3 was lower in LUAD than in the normal tissues, while its protein expression was not consistent with the mRNA level. The expression of PFKFB3 was correlated with clinicopathological parameters and several signaling pathways. The potential long chain (lnc)RNA/microRNA/PFKFB3 axis and the possible mechanism by which tumor progression in LUAD is promoted was predicted. We obtained the LINC01798/LINC02086/AP000845.1/HAGLR-miR-17-5p-PFKFB3 axis after comprehensive analyses of expression, correlation, and survival. Moreover, the expression of PFKFB3 was positively correlated with immune cells and immune checkpoint expression, including PD-1, PD-L1 and CTLA-4.

Conclusion: The present study demonstrated that noncoding RNAs mediated the upregulation of PFKFB3 and was associated with a poor prognosis and immune tumor infiltration in LUAD.

Keywords: PD-1/PD-L1; PFKFB3; lncRNA; miR-17-5p; tumor immune infiltration.

Grants and funding

This study was funded by grants from National Natural Science Foundation of China (No. 82273422) Jiangsu Graduate Research and Practice Innovation Program (SJCX21_1473, SJCX22_1639), Basic Science Research Project in Nantong City, Jiangsu, China (No.JC2021029), Nantong Municipal Science and Technology Project (No. JCZ19103), 2022 Nantong Basic Science Research Plan-Young Science and Technology Talents Innovation Special Project (No. JC12022016), 2022 Nantong City science and Technology Guidance Plan (No. JCZ2022016).