Purpose: There is a great controversy regarding the prognostic significance of epidermal growth factor receptor (EGFR) in glioma patients. The current meta-analysis was conducted to evaluate the effect of abnormal EGFR expression on overall survival in glioma patients.
Materials and methods: A comprehensive literature search of PubMed, EMBASE, Google Scholar, Web of Science, and Cochrane Library was conducted. The combined hazard ratio (HR) and its 95% confidence intervals (CIs) were used to evaluate the association between EGFR expression and survival in glioma.
Results: A total of 476 articles were screened, and 17 articles containing 1,458 patients were selected. The quality assessment of the included studies was performed by the Newcastle–Ottawa Scale. Overexpression of EGFR was found to be an indicator of poor prognosis in overall survival in glioma patients (HR =1.72, 95% CI 1.32–2.25, P=0.000, random effect) and glioblastoma multiforme patients (HR =1.57, 95% CI 1.15–2.14, P=0.004, random effect). Subgroup analysis was conducted to explore the source of high heterogeneity.
Conclusion: This meta-analysis indicated that high expression of EGFR may serve as a biomarker for poor prognosis in glioma patients.


Keywords: epidermal growth factor receptor, glioma, meta-analysis, prognosis 


INTRODUCTION

Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase on chromosome 7p12, containing an extracellular ligand-binding domain, a transmembrane domain, and an intracellular tyrosine kinase domain, belonging to the HER family. The family includes four members (HER1/EGFR, HER2/neu, HER3, and HER4), with downstream signaling pathways regulating a number of processes, including growth, migration, and survival.1 The pathway is involved in the development and progression of several human malignancies, including non-small-cell lung cancer, gastric cancer, pancreatic cancer, and nasopharyngeal carcinoma.2–6

Glioma is the most common primary malignancy of the central nervous system, accounting for over half of all malignant brain tumors in adults.7 According to the WHO grading (2016), glioma can be divided into four grades. Glioblastoma multiforme (GBM) has the highest grade and the greatest malignancy. The median survival after standard treatment is ~13 months. Median progression-free survival (PFS) is only 7.2 months.8 The EGFR gene is one of the earliest known carcinogenic genes found in GBM. Its increased transcriptional activity directly causes EGFR expression.9 Due to its pro-oncogenic effects, it is not surprising that increased EGFR expression is associated with the malignancy of glioma.10 A study has found that serum levels of EGFR are substantially increased in patients with malignant glioma, suggesting poor survival.11

It has been hypothesized that EGFR may be a potential prognostic biomarker for glioma. However, there remains some controversy as to the prognostic value of EGFR in glioma. Because of the limitations of sample size and research methods, individual studies have not reached consensus on the question. Therefore, this meta-analysis was conducted to evaluate the effect of abnormal EGFR expression on overall survival (OS) in glioma patients.