Upregulation of FEN1 Is Associated with the Tumor Progression and Prognosis of Hepatocellular Carcinoma.

Yingying Zhang,Chen Xue,Jianan Chen,Siyu Chen,Liwen Liu,Yongjian Zhou,Xin Liu,Shen Shen,Qiuyue Hu,Guangying Cui,Zujiang Yu

doi:10.1155/2020/2514090

Yingying Zhang, Chen Xue + Show 9 more

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https://doi.org/10.1155/2020/2514090

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Abstract

Background Studies show that patients with hepatocellular carcinoma (HCC) have poor prognosis, particularly when patients are diagnosed at late stages of the disease development. The flap endonuclease 1 (FEN1) gene is overexpressed in multiple malignant tumors and may promote tumor aggressiveness. However, its expression profile and functional roles in HCC are still unclear. Here, we evaluated the molecular mechanisms of FEN1 in HCC. Methods The expression of FEN1 in HCC was evaluated using HCC mRNA expression data from TCGA and GEO databases. The expression of FEN1 was also confirmed by immunohistochemistry (IHC) using a tissue microarray (TMA) cohort with a total of 396 HCC patients. Kaplan-Meier analysis and univariate and multivariate Cox regression analyses were used to determine the correlation between FEN1 expression and survival rate of HCC patients. The molecular mechanism and biological functions of FEN1 in HCC were predicted using functional and pathway enrichment analysis in vitro experiments. Results FEN1 was overexpressed in multiple HCC cohorts at both mRNA and protein levels. The receiver operating characteristic (ROC) curve showed that FEN1 can serve as a diagnostic predictor of HCC. Meanwhile, patients with high FEN1 expression levels showed lower overall survival (OS) and relapse-free survival (RFS) rates than those with low FEN1 expression. More importantly, we found that FEN1 elevation was an independent prognostic factor for OS and RFS in HCC patients based on univariate and multivariate analyses, indicating that FEN1 might be a potential prognostic marker in HCC. Furthermore, knocking down FEN1 resulted in suppressed cell proliferation and migration in vitro. This could have been due to regulation expressions of c-Myc, survivin, and cyclin D1 genes, indicating that FEN1 may function as an oncogene through its role in the cell cycle and DNA replication pathway. Conclusion Our study indicated that high FEN1 expression might function as a biomarker for diagnosis and prognosis. In addition, the study confirms that FEN1 is an oncogene in HCC progression.

Highlights

Deaths resulting from hepatocellular carcinoma (HCC) have risen in the past decade necessitating numerous research activities across the world focusing on this condition [1]
Pan-cancer data downloaded from The Cancer Genome Atlas (TCGA) database were used to evaluate flap endonuclease 1 (FEN1) mRNA expression levels
Analysis of protein expression in the pancancer tissue microarray (TMA) showed a high FEN1 expression in HCC compared to adjacent normal tissues (Figures 1(b) and 1(c))

Summary

Introduction

Deaths resulting from hepatocellular carcinoma (HCC) have risen in the past decade necessitating numerous research activities across the world focusing on this condition [1]. HCC patients are often diagnosed during advanced stages of disease development rendering them ineligible for surgery because of insidious onset and early metastasis [3]. To counter this problem and boost chances of survival in these patients, biomarkers for early diagnosis and prediction of recurrence of the disease are urgently needed. Knocking down FEN1 resulted in suppressed cell proliferation and migration in vitro This could have been due to regulation expressions of c-Myc, survivin, and cyclin D1 genes, indicating that FEN1 may function as an oncogene through its role in the cell cycle and DNA replication pathway. The study confirms that FEN1 is an oncogene in HCC progression

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Conclusion