AUTHOR=Han Jiahui , Deng Xinzhou , Sun Renhuang , Luo Ming , Liang Meng , Gu Bing , Zhang Te , Peng Zhen , Lu Ying , Tian Chao , Yan Yutao , Luo Zhiguo TITLE=GPI Is a Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.752642 DOI=10.3389/fonc.2021.752642 ISSN=2234-943X 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.