Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China

Jiao, Xingyuan; Ying, Wei; Zhou, Liansuo; He, Jing; Yang, Chonghua; Zhang, Peng; Hu, Ronglin; Luo, Chen; Du, Jun; Fu, Junfen; Shi, Jinsen; He, Rui; Li, Dongming; Wang, Jun

doi:10.1038/srep18160

Cited by 15 publications

(20 citation statements)

References 51 publications

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“…In vitro experiments 15 Disease Markers proved that silencing FEN1 inhibited cell proliferation and migration by regulating expressions of c-Myc, survivin, and cyclin D1. These findings are consistent with previously reported roles of FEN1 in both DNA replication and repair [5]. Collectively, our results indicated that the potential mechanism of FEN1 action in HCC might be regulating the cell cycle and DNA replication pathway.…”

Section: Disease Markerssupporting

confidence: 93%

“…Particularly, inappropriate DNA repair can cause malignant transformation of cells by activating oncogenes or inactivating tumor suppressors [4]. Flap endonuclease 1 (FEN1), a structure-specific multifunctional enzyme, plays a pivotal role in both DNA replication and repair [5]. Previous studies have demonstrated that FEN1 single-nucleotide polymorphisms (SNPs) are involved in various cancer developments, including breast cancer [6], lung cancer [4,7], hepatocellular carcinoma [8], esophageal cancer [9], and gastric cancer [10] as well as glioma [11].…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2020

Disease Markers

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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.

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Section: Disease Markerssupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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

Zhang

Liu

et al. 2020

Disease Markers

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“…8 FEN1 −69G>A and +4150G>TG polymorphisms were shown to be significantly associated with glioma 10 and gallbladder cancer. 17 Lv et al 11 reported that both F I G U R E 6 Sensitivity analysis of the overall ORs for the FEN1-69G>A polymorphism. The results were calculated through omitting each eligible study.…”

Section: Discussionmentioning

confidence: 99%

Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta‐analysis

Moazeni‐Roodi

Ghavami

Ansari

et al. 2019

J of Cellular Biochemistry

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Flap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 −69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta-analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta-analysis. Overall, meta-analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta-analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings. K E Y W O R D Scancer, flap endonuclease 1, meta-analysis, polymorphism

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“…For example, most studies that determined whether APE1 can be used as a predictive marker showed that high level expression or cytoplasmic staining were associated with poor outcomes and resistance to chemoradiotherapy in patients with lung cancer, breast cancer, head and neck cancer, osteosarcomas, germ cell tumors and hepatocellular carcinomas [ 19 ]. Jiao et al revealed that FEN1 was associated with the risk of gallbladder cancer [ 20 ]. Dicer expression might also be an indicator of prognosis for chronic lymphocytic leukemia [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a detection assay for DNA endonuclease activity and its application in the screening and prognosis of malignant lymphoma

Wang²,

et al. 2018

BMC Biochem

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BackgroundEndonucleases play critical roles in maintaining genomic stability and regulating cell growth. The purpose of this study was to evaluate detection of endonuclease activity as an indicator in the early diagnosis and prognosis of lymphoma.ResultsThe method of endonuclease activity determination was successfully established and applied to compare cancer patient and control cohorts. Endonuclease activities of cancer tissues were significantly higher than those of adjacent control tissues (P < 0.001). We next investigated endonuclease activity in peripheral blood of enrolled patients and the controls, which were also significantly higher in patients than in controls (P = 0.015). Additionally, endonuclease activities were elevated in the metastasis subgroup compared with the non-metastasis subgroup(P = 0.038), whereas no significant difference was found between age(≤ 56y, > 56y) and gender (P = 0.736 > 0.05 and P = 0.635 > 0.05, respectively). Although there was no significant difference between control group with the non-metastatic cancer patients (P = 0.800 > 0.05), endonuclease activities were lower in the control group compared with the non-metastatic cancer patients with lymphoma (P = 0.033). The progression-free survival probability of patients with elevated R ratios(R ratio ≥ 1.4) was significantly lower than that of patients with lower R ratios (R ratio < 1.4).ConclusionsAn assay was established to detect the endonuclease activity,which might be useful for the prognosis of cancers, especially lymphoma.

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Variants and haplotypes in Flap endonuclease 1 and risk of gallbladder cancer and gallstones: a population-based study in China

Cited by 15 publications

References 51 publications

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

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

Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta‐analysis

Establishment of a detection assay for DNA endonuclease activity and its application in the screening and prognosis of malignant lymphoma

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