Early 2 factor (E2F) transcription factors contribute to malignant progression and have clinical prognostic value in lower-grade glioma

ABSTRACT

Early 2 factor (E2F) genes encoding a family of transcription factors are significantly associated with apoptosis, metabolism, and angiogenesis in several tumor types. However, the biological functions of E2F transcription factors (E2Fs) and their potential involvement in the malignancy of lower-grade glioma (LGG) remain unclear. We explored the effects of the expression of eight E2F family members on the clinical characteristics of LGG based on the Chinese Glioma Genome Atlas (CGGA), The Cancer Genome Atlas (TCGA), and GSE16011 datasets. Two LGG subgroups were identified according to the consensus clustering of the eight E2Fs. We employed the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm for further functional experiments and the development of a potential risk score. Two categories of patients with LGG were identified based on the median risk scores. We then developed a nomogram based on the results of the multivariate analysis. Real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry were performed to validate the bioinformatics results. Our results indicated that E2F family members were significantly involved in the malignancy of LGG and might serve as effective prognostic biomarkers of the disease.

KEYWORDS:

• E2F transcription factors
• lower-grade glioma
• risk model
• overall survival
• gene expression profile

Highlights

1. The correlations between E2Fs expression and LGG malignancy were explored.

2. A risk signature of four E2Fs was an independent prognostic index for LGG prognosis.

3. The bioinformatics results were validated by RT-qPCR and immunohistochemistry assays.

Data availability statement

Data for this work were obtained from the CGGA (http://www.cgga.org.cn/), TCGA (https://portal.gdc.cancer.gov/), GSE16011 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE16011), ONCOMINE (https://www.oncomine.org/), and Human Protein Atlas datasets (https://www.proteinatlas.org/).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval

Our study was approved by the Ethics Committee of the second affiliated hospital of Nanchang University. The Examination and Approval No. Review [2016] No. (122).

Supplementary material

Supplemental data for this article can be accessed here

Author’s contributions

Haitao Luo was involved in conception and design and Chuming Tao in data acquisition, Xiaoyan Long performed the RT-qPCR and immunohistochemistry assays. Kai Huang and Xingen Zhu drafted the manuscript and contributed to the revision. All authors edited and approved the final version of manuscript.

Additional information

Funding

This study was supported by National Natural Science Foundation of China (Grant no: 82002660 and 81660420); and Jiangxi Province Department of Education Science and technology research project (Grant no. GJJ190018).National Natural Science Foundation of China [82002660];National Natural Science Foundation of China [Grant no: 81660420]; Key Science and Technology Research Project in Jiangxi Province Department of Education [Grant no. GJJ190018].