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Published on: June 27, 2020
Comprehensive bioinformatics analysis of the E2F family in human clear cell renal cell carcinoma
Zhi-Guo Liu1, Jing Su2, Hao Liu3
1Department of Hospital Pharmacy, The Affiliated Suqian First People's Hospital of Nanjing Medical University, Suqian, Jiangsu 223800, P.R. China.
Abstract:
Clear cell renal cell carcinoma (ccRCC) originates from renal tubular epithelial cells and is the most common pathological renal cell carcinoma type with the worst prognosis. The relationship between the expression, prognosis and mechanism of ccRCC and the E2F family remains challenging. In the present study, RNA sequencing and clinical data of ccRCC from The Cancer Genome Atlas and two datasets, GSE36895 and GSE53757, from the Gene Expression Omnibus were used to identify the role of the E2F family in ccRCC. A total of 10 groups of tumor tissues and paired-normal tissues from patients with ccRCC were verified by reverse transcription-quantitative PCR. the expression, tumor grade and stage, prognosis and regulatory mechanism of the E2F family in ccRCC were analyzed. It was found that the expression levels of E2F1 to 4 and 6 to 8 were higher in ccRCC tissues than in normal tissues, whereas the expression level of E2F5 was lower in the former than in the latter. The expression levels of E2F1 to 8 were correlated with tumor stage and grade. Low expression of E2F1 to 5 and 7 to 8 was significantly associated with longer overall survival, disease-specific survival and progression-free survival times. The data revealed that the E2F family rarely has genetic mutations. The expression of E2F1, E2F2, E2F5, E2F7 and E2F8 was significantly correlated with DNA methylation, and E2F1 to E2F7 were significantly correlated with copy number and the data showed that the expression of E2Fs was significantly correlated with the cell cycle. The results of the present study suggested that E2F family genes may be potential targets for ccRCC molecular diagnosis and targeted therapy.
Insights
This study reveals that E2F family gene expression is altered in clear cell renal cell carcinoma (ccRCC). Lower expression of most E2F genes correlates with better patient survival, suggesting they are potential diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer with a poor prognosis.
- The role of the E2F family in ccRCC, including its expression, prognostic value, and underlying mechanisms, requires further elucidation.
Purpose of the Study:
- To investigate the expression patterns of the E2F family in ccRCC.
- To analyze the correlation between E2F family expression and clinical parameters, prognosis, and regulatory mechanisms in ccRCC.
Main Methods:
- Utilized RNA sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE36895, GSE53757).
- Validated gene expression using reverse transcription-quantitative PCR (RT-qPCR) on patient tissues.
- Analyzed correlations with tumor grade, stage, survival, DNA methylation, copy number, and cell cycle regulation.
Main Results:
- E2F1-4 and E2F6-8 expression was higher, while E2F5 expression was lower in ccRCC tissues compared to normal tissues.
- E2F family expression levels correlated with tumor stage and grade.
- Downregulation of E2F1-5 and E2F7-8 was significantly associated with improved overall survival, disease-specific survival, and progression-free survival.
- E2F family genes showed minimal mutations but significant correlations with DNA methylation, copy number alterations, and cell cycle regulation.
Conclusions:
- The E2F family plays a significant role in ccRCC development and progression.
- Aberrant E2F expression is linked to patient prognosis in ccRCC.
- E2F family genes represent promising candidates for molecular diagnosis and targeted therapy in ccRCC.
