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

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

doi:10.3389/fonc.2021.752642

Abstract

BackgroundGlucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. However, the role of GPI in lung adenocarcinoma (LUAD) remains unclear.MethodsAll 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.ResultsIn 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.ConclusionGPI 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.

Highlights

Lung cancer is one of the malignant cancers with the highest incidence and the worst prognosis worldwide
To better understand the role of the Glucose-6-phosphate isomerase (GPI) gene in non-small-cell lung cancer (NSCLC), we comprehensively evaluated the relationship between GPI expression and the prognosis of Lung adenocarcinoma (LUAD) patients through The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Oncomine, and Kaplan–Meier plotter databases
The results showed that, compared with that in normal tissues, GPI expression was significantly higher in tumor tissues such as bladder cancer, colorectal cancer, gastric cancer, kidney cancer, lung cancer, ovarian cancer, and lymphoma

Summary

Introduction

Lung cancer is one of the malignant cancers with the highest incidence and the worst prognosis worldwide. Lung cancer is divided into small cell lung cancer and non-small-cell lung cancer (NSCLC) [1, 2]. Lung adenocarcinoma (LUAD) is the largest subgroup of NSCLC [3]. New therapies have been created for NSCLC, including surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy [4]. The recurrence rate and mortality rate of LUAD are still high, and the prognosis of patients is poor. It is imperative to find more effective biomarkers to facilitate novel therapeutic methods. Glucose-6-phosphate isomerase (GPI) plays an important role in glycolysis and gluconeogenesis. The role of GPI in lung adenocarcinoma (LUAD) remains unclear

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Results

Conclusion