Bioinformatics analysis of circRTN4IP1 in hepatocellular carcinoma and its relationship with clinical prognosis

doi:10.3877/cma.j.issn.2095-3232.2021.03.021

Abstract

Abstract:

Objective

To explore the expression of circular RNA circRTN4IP1 in hepatocellular carcinoma (HCC) and its relationship with clinical prognosis.

Methods

GEO datasets of GSE 97332, GSE 94508 and GSE 78520 were analyzed using Limma package of R software, and the differentially-expressed circular RNAs were screened. The combining microRNAs (miRNAs) of circRTN4IP1 were predicted on CSCD website. The target genes of miRNA were jointly predicted through TargetScan, miRDB and miRTarBase databases and then subjected to gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The function of target genes and protein-protein interaction (PPI) network were analyzed using STRING online tool, and the key genes were selected. The relationship between the genes and prognosis was analyzed by Kaplan-Meier Plotter database. The cancer tissues and paired adjacent tissues were collected from 60 HCC patients who underwent surgical resection in Sun Yat-sen Memorial Hospital of Sun Yat-sen University from August 2016 to June 2018. The expression level of circRTN4IP1 in the tissues was detected by fluorescence quantitative RT-PCR, and its relationship with the clinicopathological features and prognosis of HCC patients was analyzed. The relative expression levels of circRTN4IP1 mRNA were compared between two groups by t test, and the rate was statistically compared by Chi-square test. Survival analysis was performed with Kaplan-Meier method and Log-rank test.

Results

Significantly up-regulated circRTN4IP1 in HCC was screened out by GEO datasets and its 60 combining miRNAs and 581 target genes were found. GO and KEGG analysis showed that the target genes were mainly involved in the transcription, translation, protein ubiquitination, cell cycle and other biological processes, as well as the p38MAPK, PI3K/AKT, FoxO and TGF-β/Smad signaling pathways. 8 key genes were selected. The overall survival of HCC patients with high expression of UBE2D1, H2AFX, UBE2V1, LRRC41 and POLR2D was significantly shorter than that of HCC patients with low expression of these genes (HR=1.61, 1.93, 1.72, 1.88, 1.51; P<0.05). Fluorescence quantitative RT-PCR demonstrated that the average relative expression of circRTN4IP1 mRNA in HCC tissues was 0.759±0.020, significantly higher than 0.625±0.024 in adjacent tissues (t=8.385, P<0.05). The expression level of circRTN4IP1 was significantly correlated with the AFP level in HCC tissues (χ²=4.267, P<0.05). The disease-free survival of patients with high circRTN4IP1 expression was significantly worse compared with their counterparts with low circRTN4IP1 expression (χ²=5.055, P<0.05).

Conclusions

circRTN4IP1 is highly expressed in HCC patients, which participates in regulating the incidence and development of HCC probably by up-regulating the target genes of UBE2D1, H2AFX, UBE2V1, LRRC41 and POLR2D. circRTN4IP1 is a potential prognostic marker and therapeutic target.

Key words: Carcinoma, hepatocellular, Circular RNA, Prognosis, Computational biology

Yingcheng Wei, Liyun Huo, Wenliang Tan, Xinming Chen, Yajin Chen, Changzhen Shang. Bioinformatics analysis of circRTN4IP1 in hepatocellular carcinoma and its relationship with clinical prognosis[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2021, 10(03): 331-336.

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References 20

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