Expression of IER3 in hepatocellular carcinoma: clinicopathology, prognosis, and potential regulatory pathways.

Autor:	He FY; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Chen G; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., He RQ; Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Huang ZG; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Li JD; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Wu WZ; Department of Pathology, People's Hospital of Ling Shan, Ling Shan, Guangxi Zhuang Autonomous Region, P.R. China., Chen JT; Department of Pathology, People's Hospital of Ling Shan, Ling Shan, Guangxi Zhuang Autonomous Region, P.R. China., Tang YL; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Li DM; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Pan SL; Department of Pathophysiology, School of Pre-clinical Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Feng ZB; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China., Dang YW; Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, P.R. China.
Jazyk:	angličtina
Zdroj:	PeerJ [PeerJ] 2022 Mar 10; Vol. 10, pp. e12944. Date of Electronic Publication: 2022 Mar 10 (Print Publication: 2022).
DOI:	10.7717/peerj.12944
Abstrakt:	Background: Immediate early response 3 (IER3) is correlated to the prognosis of several cancers, but the precise mechanisms underlying the regulation by IER3 of the occurrence and development of hepatocellular carcinoma (HCC) remain unknown. Methods: The expression level of IER3 was examined by using in-house immunohistochemistry (IHC), public gene chip, and public RNA-sequencing (RNA-seq). The standardized mean difference (SMD) was calculated to compare the expression levels of IER3 between HCC patients and controls. The summary receiver operating characteristics (sROC) was plotted to comprehensively understand the discriminatory capability of IER3 between HCC and non-HCC group. The Kaplan-Meier curves and the combined hazard ratios (HRs) were used to determine the prognostic value of IER3 in HCC. Moreover, differentially expressed genes (DEGs) and co-expression genes (CEGs) were used to explored the molecular mechanisms of IER3 underlying HCC. hTFtarget was used to predict the transcription factors (TFs) of IER3. The binding site of TFs and the IER3 promoter region was forecasted using the JASPAR website. The relevant ChIP-seq data were used to determine whether TF peaks were present in the IER3 transcription initiation. Results: A significantly increased expression of IER3 protein was found in HCC tissue relative to non-HCC tissue as detected by IHC ( p  < 0.001). Compared to 1,263 cases of non-HCC tissues, IER3 in 1483 cases of HCC tissues was upregulated (SMD = 0.42, 95% confidence interval [CI] [0.09-0.76]). The sROC showed that IER3 had a certain ability at differentiating HCC tissues (area under the curve (AUC) = 0.65, 95% CI [0.61-0.69]). Comprehensive analysis of the effect of IER3 on the prognosis of patients with HCC demonstrated that higher IER3 expression was associated with poor prognosis in HCC (HRs = 1.30, 95% CI [1.03-1.64]). Pathway enrichment analysis revealed that IER3-related genes were mostly enriched in the PI3K-Akt signaling pathway, cancer-related signaling pathways, the p53 signaling pathway, and other signaling pathways. Regulatory factor X5 (RFX5) was identified as a possible regulator of IER3-related TF. Conclusion: IER3 may be a potential prognostic marker for HCC. The molecular mechanisms of IER3 in HCC warrant further study. Competing Interests: Gang Chen is an Academic Editor for PeerJ. (©2022 He et al.)
Databáze:	MEDLINE
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