Predictive role of E2F6 in cancer prognosis and responses of immunotherapy

Chuandong Gong; Zewei Tu; Xiaoyan Long; Xinjun Liu; Feng Liu; Jia Liu; Xingen Zhu; Jingying Li; Kai Huang

doi:10.1016/j.intimp.2023.111302

Predictive role of E2F6 in cancer prognosis and responses of immunotherapy

Int Immunopharmacol. 2024 Jan 25:127:111302. doi: 10.1016/j.intimp.2023.111302. Epub 2023 Dec 9.

Authors

Chuandong Gong¹, Zewei Tu¹, Xiaoyan Long², Xinjun Liu³, Feng Liu⁴, Jia Liu⁵, Xingen Zhu⁶, Jingying Li⁷, Kai Huang⁸

Affiliations

¹ Department of Neurosurgery, the 2(nd) affiliated hospital, Jiangxi Medical College, Nanchang University, Jiangxi 330006, PR China; Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang, Jiangxi 330006, PR China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi 330006, PR China; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi 330006, PR China.
² East China Institute of Digital Medical Engineering, Shangrao, Jiangxi 330006, PR China.
³ People's Hospital of Yingtan City, Yingtan, Jiangxi 330006, PR China.
⁴ Department of Neurosurgery, Jiangxi Provincial Children's Hospital, Nanchang, Jiangxi 330006, PR China.
⁵ Department of Neuroscience, Yale School of Medicine, New Haven, CT 06511, USA.
⁶ Department of Neurosurgery, the 2(nd) affiliated hospital, Jiangxi Medical College, Nanchang University, Jiangxi 330006, PR China; Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang, Jiangxi 330006, PR China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi 330006, PR China; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi 330006, PR China. Electronic address: ndefy89006@ncu.edu.cn.
⁷ Department of Comprehensive Intensive Care Unit, the 2(nd) affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China. Electronic address: jingyingli@ncu.edu.cn.
⁸ Department of Neurosurgery, the 2(nd) affiliated hospital, Jiangxi Medical College, Nanchang University, Jiangxi 330006, PR China; Jiangxi Key Laboratory of Neurological Tumors and Cerebrovascular Diseases, Nanchang, Jiangxi 330006, PR China; Institute of Neuroscience, Nanchang University, Nanchang, Jiangxi 330006, PR China; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi 330006, PR China. Electronic address: kaihuang@ncu.edu.cn.

PMID: 38071912
DOI: 10.1016/j.intimp.2023.111302

Abstract

Background: E2F6 is a member of the E2F transcription factor family. Numerous studies have demonstrated that E2F6 is critical to cancer development and progression, but its role in cancer immunotherapy remains unclear.

Methods: Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases were used to obtain RNA-seq data for cancer and normal tissues, and we utilized the cBioPortal to analyze E2F6 genomic alterations in pan-cancer. The protein localization of E2F6 was obtained using the Human Protein Atlas (HPA), and the upregulation of E2F6 expression in clinical glioblastoma multiforme (GBM) tissues was detected by Western blot analysis. The ComPPI website was used to analyze the protein interaction information of E2F6. To evaluate the role of E2F6 in pan-cancer prognosis, we used univariate Cox regression and Kaplan-Meier methods, and gene set enrichment analysis (GSEA) was utilized to identify markers associated with E2F6 expression in tumors. TIMER 2.0 was used to study E2F6-related immune cell infiltration in tumor tissues, and the correlation of E2F6 with immunotherapy biomarkers was investigated using Spearman correlation analysis. The role of E2F6 in the cell cycle was analyzed by flow cytometry, and the Cell Counting Kit-8 (CCK-8) and colony formation assays were utilized to determine the proliferative ability of cells.

Results: In most tumor types, E2F6 was highly expressed and was a good predictor of prognosis. E2F6 was significantly related to markers of immune activation, tumor immune cell infiltration, and immune regulators. Furthermore, E2F6 knockdown significantly attenuated the proliferative ability of glioma cells. Finally, E2F6 effectively predicted anti-programmed cell death 1 (PD1) treatment response.

Conclusion: E2F6 is an effective biomarker that predicts the prognosis of cancer patients treated with anti-immune checkpoint therapy.

Keywords: Cancer immunotherapy; E2F6; Immunotherapy response; Pan-cancer; Prognostic biomarker.

MeSH terms

Biological Assay
Blotting, Western
Cell Count
E2F6 Transcription Factor
Humans
Immunotherapy*
Neoplasms* / therapy
Prognosis
Tumor Microenvironment

Substances

E2F6 protein, human
E2F6 Transcription Factor