BRD4 inhibitor JQ1 may affect the prognosis of cervical cancer through super-enhancer-related genes
1The Second Clinical Medical College of Fujian Medical University, The Second Affiliated Hospital of Fujian Medical University, 362000 Quanzhou, Fujian, China
2Department of Obstetrics and Gynecology, Quanzhou Medical College People’s Hospital Affiliated, 362000 Quanzhou, Fujian, China
3Department of Obstetrics and Gynecology, The First People’s Hospital of Foshan, 528000 Foshan, Guangdong, China
4Department of Gynecology, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 350000 Fuzhou, Fujian, China
5Department of Radiation Oncology, The Second Affiliated Hospital of Fujian Medical University, 362000 Quanzhou, Fujian, China
DOI: 10.22514/ejgo.2023.076 Vol.44,Issue 5,October 2023 pp.26-38
Submitted: 01 December 2022 Accepted: 14 February 2023
Published: 15 October 2023
† These authors contributed equally.
To explore the effects of bromine domain protein 4 (BRD4) inhibitor JQ1 on the expression profile of super-enhancer-related genes (SE-genes) in cervical cancer (CC) HeLa cells and construct a prognosis model to explore the potential impact of JQ1 on the prognosis of CC. Whole transcriptome sequencing technology was used to detect changes in the gene expression profiles of JQ1-treated and control cells. Differentially expressed SE-genes were identified by matching via the dbCoRC database and Cistrome Data Browser (Cistrome DB). The prognosis of differentially expressed SE-genes was analyzed in the Cancer Genome Atlas (TCGA) dataset based on gene expression status. The Cox proportional risk model and least absolute shrinkage and selection operator (LASSO) regression were used to construct the prognostic model. A total of 1161 SE-genes were identified from dbCoRC and Cistrome DB, among which 1004 SE-genes were successfully matched to the expression profiles of JQ1 transcriptome sequencing. Differential expression analysis identified 110 differentially expressed SE-genes, among which 72 were down-regulated and 38 were upregulated. Then, a 9 SE-gene prognostic model was constructed, and Kaplan-Meier (K-M) curves showed that the high-risk group had significantly poorer clinical survival outcomes (p < 0.05). Time-dependent receiver operating characteristic (ROC) curves showed that the 1-year, 2-year and 3-year survival estimation of the proposed model was 0.82, 0.86 and 0.87, respectively, demonstrating excellent performance. JQ1 significantly impacts the SE-genes expression profile of HeLa cells, and the proposed model based on 9 differentially expressed SE-genes may effectively predict the survival outcomes of CC patients. As this study was based on exploratory analysis, further prospective studies are needed to verify the effectiveness of the SE-genes-based prognostic model.
BRD4 inhibitor; Cervical cancer; Super-enhancer related genes; JQ1; HeLa cells; RNA-Seq
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