GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma

Jiahui Han; Xinzhou Deng; Renhuang Sun; Ming Luo; Meng Liang; Bing Gu; Te Zhang; Zhen Peng; Ying Lu; Chao Tian; Yutao Yan; Zhiguo Luo

doi:10.3389/fonc.2021.752642

GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma

Front Oncol. 2021 Nov 29:11:752642. doi: 10.3389/fonc.2021.752642. eCollection 2021.

Authors

Jiahui Han^{1

2}, Xinzhou Deng^{3

4}, Renhuang Sun³, Ming Luo³, Meng Liang³, Bing Gu⁵, Te Zhang⁶, Zhen Peng³, Ying Lu³, Chao Tian³, Yutao Yan³, Zhiguo Luo^{1

3}

Affiliations

¹ Department of Clinical Oncology, Taihe Hospital, Jinzhou Medical University Union Training Base, Shiyan, China.
² Department of Clinical Medicine, The First Clinical College of Hubei University of Medicine, Shiyan, China.
³ Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
⁴ Hubei Key Laboratory of Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
⁵ Department of Oncology, Danjiangkou First Hospital, Danjiangkou, China.
⁶ Biomedical Research Institute, Hubei University of Medicine, Shiyan, China.

Abstract

Background: Glucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. However, the role of GPI in lung adenocarcinoma (LUAD) remains unclear.

Methods: All original data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and integrated via R 3.2.2. GPI expression was explored with TCGA, GEO, and Oncomine databases. Immunohistochemistry staining was used to analyze GPI expression in clinical specimens. The correlations between GPI and cancer immune characteristics were analyzed via the TIMER and TISIDB databases. GPI-specific siRNAs were used to verify the role of GPI expression on cell proliferation and cell cycle distribution.

Results: In general, GPI is predominantly overexpressed and has reference value in the diagnosis and prognostic estimation of LUAD. Upregulated GPI was associated with poorer overall survival, clinical stage, N stage, and primary therapy outcome in LUAD. Mechanistically, we identified a hub gene that included a total of 56 GPI-related genes, which were tightly associated with the cell cycle pathway in LUAD patients. Knockdown of GPI induced cell proliferation inhibition and cell cycle arrest. GPI expression was positively correlated with infiltrating levels of Th2 cells and regulatory T cells (Tregs); in contrast, GPI expression was negatively correlated with infiltrating levels of CD8⁺ T cells, central memory T cells, dendritic cells, macrophages, mast cells, and eosinophils. GPI was negatively correlated with the expression of immunostimulators, such as CD40L, IL6R, and TMEM173, in LUAD.

Conclusion: GPI may play an important role in the cell cycle and can be used as a prognostic biomarker for determining the prognosis and immune infiltration in LUAD.

Keywords: cell cycle; glucose-6-phosphate isomerase (GPI); immune infiltrate; lung adenocarcinoma; prognosis (carcinoma).