Diagnostic and prognostic utility of eIF6 in glioblastoma: a study based on TCGA and CGGA databases

Abstract

Background: Among various glioma types, glioblastoma multiforme (GBM) is one of those with the highest malignancy. Although overexpression of eukaryotic translation initiation factor 6 (eIF6), a factor that regulates protein translation initiation, is believed to promote tumor development, its function and potential molecular mechanisms in glioma progression remain uncharacterized. Consequently, we evaluated its diagnostic and prognostic utility in GBM patients.

Methods: Sample data from two databases, The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), were utilized to investigate the role of eIF6 as well as its mechanism of action in gliomas. We analyzed eIF6 expression in normal tissues as well as cancerous samples of different stages of glioma. The diagnostic and prognostic value of eIF6 were analyzed using the Receiver Operating Characteristic Curve (ROC) and Kaplan-Meier analysis, respectively. Furthermore, its underlying molecular mechanism in GBM was further revealed by gene set enrichment analysis (GSEA).

Results: Transcriptome data analyses of the two databases showed that eIF6 was upregulated in glioma tissues compared with normal counterparts. eIF6 was at high levels in WHO grade IV gliomas versus grade II and III gliomas (P<0.05). In addition, eIF6 was highly expressed in elderly and Asian glioma patients. Furthermore, eIF6 expression was found to be lower in isocitrate dehydrogenase (IDH)-mutated tumors. Patients with high eIF6 level presented shorter overall survival than cases with low eIF6 level (P<0.05), and eIF6 had favorable accuracy in predicting the prognosis of glioma patients. GSEA revealed that high eIF6 expression was mainly concentrated in cell cycle and DNA repair related pathways.

Conclusions: eIF6 is highly expressed in gliomas and positively associated with the degree of malignancy. Patients with high eIF6 expression present poor survival. Therefore, eIF6 has the potential to be a diagnostic biomarker and a potential therapeutic target for glioma development and GBM.

Keywords: GSEA; eIF6; glioma; overall survival.

Figure 1

eIF6 expression in tumor tissue and normal counterparts. A. eIF6 in carcinoma tissue and normal counterparts from TCGA database; B. eIF6 in carcinoma tissue and normal counterparts from TCGA and GTEx databases.

Figure 2

Expression in carcinoma tissue specimens from TCGA database. A. Expression of eIF6 in different age groups; B. Expression of eIF6 in different genders; C. Expression of eIF6 in different races; D. Expression of eIF6 in patients with different grades of gliomas.

Figure 3

Expression of eIF6 in cancer tissue samples from CGGA database. A. Expression of eIF6 in different age groups; B. Expression of eIF6 in different genders; C. Expression of eIF6 in different IDH mutation status; D. Expression of eIF6 in patients with different WHO grades of gliomas.

Figure 4

Correlation of eIF6 expression with glioma patient’s overall survival. A. Correlation of eIF6 expression with overall survival of GBM patients in TCGA database; B. Time-dependent ROC curve of GBM patients in TCGA database; C. Correlation of eIF6 expression with overall survival of LGG patients in TCGA database; D. Time-dependent ROC curve of LGG patients in TCGA database; E. Correlation of eIF6 expression with glioma patients’ overall survival in TCGA; F. Time-dependent ROC curve in the TCGA database; G. Relationship between eIF6 expression and glioma patients’ overall survival in CGGA; H. Time-dependent ROC curve in the CGGA database.

Figure 5

Pathways involved in the eIF6 enrichment analysis. A. KEGG enrichment analysis; B. HALLMARK enrichment analysis.