Hepatitis B Virus Promotes Hepatocellular Carcinoma Progression Synergistically With Hepatic Stellate Cells via Facilitating the Expression and Secretion of ENPP2
Abstract:Background: Hepatitis B virus (HBV) infection is a major risk factor causing hepatocellular carcinoma (HCC) development, but the molecular mechanisms are not fully elucidated. It has been reported that virus infection induces ectonucleotide pyrophosphatase-phosphodiesterase 2 (ENPP2) expression, the latter participates in tumor progression. Therefore, the aim of the present study was to investigate whether HBV induced HCC malignancy via ENPP2.Methods: HCC patient clinical data were collected and prognosis was … Show more
“…Bioinformatics analysis of TCGA high-throughput RNA sequencing data revealed that the expression of ENPP2 was significantly increased in liver cancer compared to adjacent normal liver tissue, which is consistent with previous studies. [14,18] Furthermore, by integrating clinical data from TCGA, we discovered a significant correlation between abnormal expression of ENPP2 and gender and clinical grouping in liver cancer. To further investigate the prognostic significance of ENPP2 in HCC, we analyzed several outcomes using the Kaplan-Meier Plotter database.…”
Section: Discussionmentioning
confidence: 91%
“…Bioinformatics analysis of TCGA high-throughput RNA sequencing data revealed that the expression of ENPP2 was significantly increased in liver cancer compared to adjacent normal liver tissue, which is consistent with previous studies. [14,18]…”
Section: Discussionmentioning
confidence: 99%
“…Recent findings suggest that ENPP2 may contribute to the development of hepatitis B-induced HCC by enhancing ENPP2 secretion in liver cancer cells. [14] Despite these findings, the clinical significance and prognostic value of ENPP2 in HCC remains unclear.…”
Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) has been identified as a potential biomarker in lung and prostate cancers; however, its expression and clinical relevance in hepatocellular carcinoma (HCC) remain incompletely understood. This study comprehensively assessed ENPP2 expression in pan-cancer using bioinformatics. We analyzed the expression of ENPP2 mRNA in primary liver cancer and adjacent tissues of patients with HCC using data from the TCGA database. Cox regression and Kaplan–Meier methods were used to identify clinicopathological factors associated with survival, and the diagnostic value of ENPP2 expression was evaluated using receiver operating characteristic curve analysis. We also validated our findings by performing real-time PCR on clinical liver cancer samples. Furthermore, we conducted gene set enrichment analysis using the Cancer Genome Atlas dataset to gain additional insights into the biological significance of ENPP2 in HCC. High ENPP2 expression in HCC patients is associated with gender and clinical stage, and is a significant prognostic factor for worse outcomes. ENPP2 expression is an independent risk factor for progression-free and disease-specific survival in both cohorts, suggesting its potential as an HCC biomarker. ENPP2’s diagnostic value in HCC patients was confirmed by the area under the receiver operating characteristic curve, which was 0.806. real-time PCR analysis validated the higher expression of ENPP2 in clinical liver cancer tissues. Gene set enrichment analysis identified pathways enriched in HCC patients with high ENPP2 expression, including those related to the cell cycle, MTOR and T cell receptor signaling, and phosphatidylinositol signaling systems. We have demonstrated that ENPP2 is highly expressed in HCC and is a potential independent molecular marker for the diagnosis and prognosis of HCC.
“…Bioinformatics analysis of TCGA high-throughput RNA sequencing data revealed that the expression of ENPP2 was significantly increased in liver cancer compared to adjacent normal liver tissue, which is consistent with previous studies. [14,18] Furthermore, by integrating clinical data from TCGA, we discovered a significant correlation between abnormal expression of ENPP2 and gender and clinical grouping in liver cancer. To further investigate the prognostic significance of ENPP2 in HCC, we analyzed several outcomes using the Kaplan-Meier Plotter database.…”
Section: Discussionmentioning
confidence: 91%
“…Bioinformatics analysis of TCGA high-throughput RNA sequencing data revealed that the expression of ENPP2 was significantly increased in liver cancer compared to adjacent normal liver tissue, which is consistent with previous studies. [14,18]…”
Section: Discussionmentioning
confidence: 99%
“…Recent findings suggest that ENPP2 may contribute to the development of hepatitis B-induced HCC by enhancing ENPP2 secretion in liver cancer cells. [14] Despite these findings, the clinical significance and prognostic value of ENPP2 in HCC remains unclear.…”
Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) has been identified as a potential biomarker in lung and prostate cancers; however, its expression and clinical relevance in hepatocellular carcinoma (HCC) remain incompletely understood. This study comprehensively assessed ENPP2 expression in pan-cancer using bioinformatics. We analyzed the expression of ENPP2 mRNA in primary liver cancer and adjacent tissues of patients with HCC using data from the TCGA database. Cox regression and Kaplan–Meier methods were used to identify clinicopathological factors associated with survival, and the diagnostic value of ENPP2 expression was evaluated using receiver operating characteristic curve analysis. We also validated our findings by performing real-time PCR on clinical liver cancer samples. Furthermore, we conducted gene set enrichment analysis using the Cancer Genome Atlas dataset to gain additional insights into the biological significance of ENPP2 in HCC. High ENPP2 expression in HCC patients is associated with gender and clinical stage, and is a significant prognostic factor for worse outcomes. ENPP2 expression is an independent risk factor for progression-free and disease-specific survival in both cohorts, suggesting its potential as an HCC biomarker. ENPP2’s diagnostic value in HCC patients was confirmed by the area under the receiver operating characteristic curve, which was 0.806. real-time PCR analysis validated the higher expression of ENPP2 in clinical liver cancer tissues. Gene set enrichment analysis identified pathways enriched in HCC patients with high ENPP2 expression, including those related to the cell cycle, MTOR and T cell receptor signaling, and phosphatidylinositol signaling systems. We have demonstrated that ENPP2 is highly expressed in HCC and is a potential independent molecular marker for the diagnosis and prognosis of HCC.
“…Liver cancer (LC) is known as the fourth major cause of cancer‐related death, and hepatocellular carcinoma (HCC) is the most common pathological subtype, taking up 75–85% of all primary cases of LC 1 . HCC patients often have an unfavorable prognosis due to the high metastasis and recurrence rate 2 . Besides, early symptoms of HCC are insidious, and a large number of patients are already in the advanced stage when they are diagnosed, missing the optimal treatment period 3 .…”
Section: Introductionmentioning
confidence: 99%
“…metastasis and recurrence rate. 2 Besides, early symptoms of HCC are insidious, and a large number of patients are already in the advanced stage when they are diagnosed, missing the optimal treatment period. 3 In recent decades, multiple RNAs, genes, and signaling pathways have been reported to partake in the tumorigenesis and progression of HCC.…”
Circular RNAs (circRNAs) are involved in cancer progression. Nonetheless, the role and mechanism of circ_0040705 in hepatocellular carcinoma (HCC) are unclear. The aberrantly expressed circRNAs and microRNAs (miRNAs) in HCC tissues were screened by bioinformatics. Circ_0040705, miR‐557, SRY‐box transcription factor 2 (SOX2), E‐cadherin, and N‐cadherin expressions were determined using quantitative real‐time polymerase chain reaction (qRT‐PCR) or Western blot. Cell counting kit‐8 (CCK‐8), 5‐ethynyl‐2′‐deoxyuridine (EdU), and Transwell experiments were utilized to examine the changes in HCC cell growth, migration, and invasion after circ_0040475 was overexpressed or knocked down. Lung metastasis assay was used to validate the effects of circRNA_0040705 on the lung metastasis of HCC cells in vivo. Binding sequences between circ_0040705 and miR‐557 and between miR‐557 and SOX2 were verified using dual‐luciferase reporter gene experiments. The expression levels of circ_0040705 and SOX2 mRNA were markedly increased in HCC tissues, but miR‐557 expression was down‐regulated. Circ_0040705 overexpression enhanced the growth, migration, invasion, and the expressions of E‐cadherin and N‐cadherin of HCC cells and promoted lung metastasis in vivo, whereas circ_0040705 knockdown exerted the opposite effects in HCC cells. Circ_0040705 worked as a sponge for miR‐557 to down‐modulate miR‐557 expression, and miR‐557 could specifically down‐modulate SOX2 expression. Circ_0040705 facilitates HCC cell growth, migration, and invasion by down‐modulating miR‐557 expression and up‐modulating SOX2 expression.
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