APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma

Cao, Lei; Cheng, Hongwei; Jiang, Qiuxia; Li, Hui; Wu, Zhixian

doi:10.18632/aging.102913

Cited by 59 publications

(47 citation statements)

References 48 publications

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“…The data revealed that patients with lymph node invasion or distant metastasis had increased P-Rex1 expression in tumors (Figure 2B and C ). AFP is the gold standard biomarker for HCC diagnosis, and some studies have also revealed that AFP can predict prognosis during HCC treatment[ 29 , 30 ]. Thus, we also evaluated the correlation between P-Rex1 and AFP.…”

Section: Resultsmentioning

confidence: 99%

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 is a diagnostic and prognostic biomarker for hepatocellular carcinoma

Cai

Zheng

Yao

2020

WJCC

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BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (P-Rex1) was reported to be a risk factor in several cancers, including breast cancer, lung cancer, and melanoma, but its expression and role in hepatocellular carcinoma (HCC) have not yet been fully studied. AIM To explore the expression of P-Rex1 in HCC, and further evaluate its potential application in the diagnosis and prognosis of HCC, especially in hepatitis B virus (HBV)-related patients. METHODS P-Rex1 expression in HCC was evaluated by real-time-quantitative polymerase chain reaction. The expression of P-Rex1 was subjected to correlation analysis with clinical features, such as lymph node invasion, distant metastasis, HBV infection, patient's age and gender. Receiver operating characteristic analysis was used to examine the potential role of P-Rex1 as a diagnostic biomarker in HCC. Kaplan-Meier analysis was used to determine the association between P-Rex1 expression and overall survival, progression-free survival and relapse-free survival. Bioinformatic analysis was used to validate the clinical findings. RESULTS P-Rex1 expression was significantly increased in HCC tumors than adjacent tissues. The expression of P-Rex1 was higher in HCC patients with lymph node invasion, distant metastasis, HBV infection and positive alpha-fetoprotein, respectively. The receiver operating characteristic analysis showed that P-Rex1 was a diagnostic biomarker with a higher area under the curve value, especially in patients with HBV infection. Survival analysis showed that patients with higher P-Rex1 expression had a favorable survival rate, even in early-stage patients. CONCLUSION P-Rex1 expression was highly increased in HCC, and the expression level of P-Rex1 was positively correlated with tumor progression. P-Rex1 has a higher efficiency in the diagnosis of HBV-related HCC, and could also be used as a favorable prognostic factor for HCC patients.

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Section: Resultsmentioning

confidence: 99%

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 is a diagnostic and prognostic biomarker for hepatocellular carcinoma

Cai

Zheng

Yao

2020

WJCC

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“…Also, APEX1 was reported to be associated with some cancer types, including the cancers of colon, stomach, liver, kidney, and breast, as well as osteosarcoma[ 4 - 8 , 33 ]. Recent studies showed that APEX1 is an efficient biomarker for the diagnosis and prognosis of liver cancer[ 6 , 8 , 34 ]. However, the role of APEX2 in cancer is still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Apyrimidinic endodeoxyribonuclease contains two members, namely, APEX1 and APEX2[ 3 ]. Having been widely reported in the pathogenesis of many cancers, especially in liver cancer[ 4 - 8 ], APEX1 was recently identified as a new diagnostic and prognostic biomarker for liver hepatocellular carcinoma (LIHC)[ 6 , 8 ]. However, the role of APEX2 in LIHC remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Identification of APEX2 as an oncogene in liver cancer

Ru¹,

Zhu²,

Hu³

et al. 2020

WJCC

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BACKGROUND DNA damage is one of the critical contributors to the occurrence and development of some cancers. APEX1 and APEX2 are the most important molecules in the DNA damage, and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma (LIHC). However, the expression of APEX2 and its functional mechanisms in LIHC are still unclear. AIM To examine the expression of APEX2 and the potential mechanism network in LIHC. METHODS We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool. GEO datasets, including GSE14520, GSE22058, and GSE64041, were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues. Then, we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis. We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression, showing the potential mechanisms of APEX2 in LIHC. After that, we conducted Pearson correlation analysis using GEPIA2. Next, we performed quantitative polymerase chain reaction (qPCR) assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3 cells was knocked down using small interfering RNA. The role of APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC . RESULTS APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, LUAD, LUSC, READ, and STAD. APEX2 overexpression in LIHC was validated using GSE14520, GSE22058, and GSE64041 datasets. The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate, even in the AJCC T1 patients. High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis. The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology. APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication. The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling. Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC. APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells. Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC . CONCLUSION APEX2 i...

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“…As described previously ( 13 ), published data in the Oncomine™ database (oncomine.org/resource/main.html) was investigated to analyze the CLEC4M mRNA levels in unpaired non-tumor liver tissue samples and HCC tissue samples to determine the clinical importance of CLEC4M in HCC. The threshold settings were set to P<0.0001, fold change ≥2 and Gene rank=top 10%.…”

Section: Methodsmentioning

confidence: 99%

CLEC4M overexpression inhibits progression and is associated with a favorable prognosis in hepatocellular carcinoma

Gao

2020

Mol Med Rep

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Hepatocellular carcinoma (Hcc) remains the most common malignant cancer worldwide. numerous studies have indicated that c-type lectin domain family 4 member M (clec4M) is associated with tumor progression; however, the biological functions of clec4M in Hcc have not been investigated. in the present study, clec4M overexpression was observed to be associated with a favorable patient overall, relapse-free, progression-free and disease-specific survival by using the KMplot™ database. The present study then concentrated specifically on the functions of clec4M by performing cell counting kit-8 proliferation, 5-ethynyl-2'-deoxyuridine and flow cytometric assays. clec4M overexpression inhibited proliferation and enhanced apoptosis in Huh7 and Plc/PrF/5 cells. Furthermore, the results demonstrated by using western blotting that clec4M overexpression inhibited the Janus kinase 1/signal transducer and activator of transcription 3 pathway, which is involved in various types of tumors including Hcc. in conclusion, the present study reported that clec4M may be considered as a novel indicator of Hcc and may provide a theoretical basis for improving the survival of patients with Hcc.

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APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma

Cited by 59 publications

References 48 publications

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 is a diagnostic and prognostic biomarker for hepatocellular carcinoma

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 is a diagnostic and prognostic biomarker for hepatocellular carcinoma

Identification of APEX2 as an oncogene in liver cancer

CLEC4M overexpression inhibits progression and is associated with a favorable prognosis in hepatocellular carcinoma

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