Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma

Saad, Zienab M; Fouad, Yasser; Ali, Lamia H; Hassanin, Taha M

doi:10.31557/apjcp.2020.21.9.2661

Cited by 8 publications

(5 citation statements)

References 19 publications

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“…Then, analyzing proteins that were less abundant in DHD and CHD, Annexins A2 and A4 are both calcium-dependent phospholipid-binding proteins involved in exocytosis and are upregulated in different neoplasms, including hepatocellular carcinoma and liver fibrosis [35][36][37][38]. Interestingly, Annexin A4 is expressed only by epithelial cells and encodes a protein that has possible interactions with ATP, has anticoagulant activity in vitro, and also inhibits the activity of phospholipase A2, having a protective effect against inflammation [39].…”

Section: Discussionmentioning

confidence: 99%

Fecal Proteome Profile in Dogs Suffering from Different Hepatobiliary Disorders and Comparison with Controls

Cerquetella,

Mangiaterra,

Pinnella

et al. 2023

Animals

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In the present study, the fecal proteomes of clinically healthy dogs (HD = n. 10), of dogs showing clinical, ultrasonographic, and/or laboratory evidence of different hepatobiliary dysfunction (DHD = n. 10), and of dogs suffering from chronic hepatitis (CHD = n. 10) were investigated with an Ultimate 3000 nanoUPLC system, coupled to an Orbitrap Fusion Lumos Tribrid mass spectrometer. Fifty-two different proteins of canine origin were identified qualitatively in the three study groups, and quantitative differences were found in 55 proteins when comparing groups. Quantitatively, a total of 41 and 36 proteins were found differentially abundant in the DHD and CHD groups compared to the control HD, and 38 proteins resulted dysregulated in the CHD group as compared to the DHD group. Among the various proteins, differently abundant fecal fibronectin and haptoglobin were more present in the feces of healthy and DHD dogs than in chronic ones, leading us to hypothesize its possible diagnostic/monitoring role in canine chronic hepatitis. On the other hand, the trefoil factor 2 was increased in DHD dogs. Our results show that the analysis of the fecal proteome is a very promising field of study, and in the case of dogs suffering from different hepatobiliary disorders, it was able to highlight both qualitative and quantitative differences among the three groups included. Results need to be confirmed with western blotting and in further studies.

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Section: Discussionmentioning

confidence: 99%

Fecal Proteome Profile in Dogs Suffering from Different Hepatobiliary Disorders and Comparison with Controls

Cerquetella,

Mangiaterra,

Pinnella

et al. 2023

Animals

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“…The overexpression of Lewis(y), a component of the structure of the ANXA4 membrane protein, induces the chemoresistance of ovarian cancer cells, and ultimately promoting the progression of ovarian cancer (38). It was reported that the increased serum level of ANXA4 might be a promising biomarker for the early detection of hepatocellular carcinoma (39). A recent study indicated that downregulation of ANXA4 by toosendanin could mediate cisplatin sensitization in non-small cell lung cancer (40).…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4

Yan

Zhu

Shi

et al. 2021

Front. Cardiovasc. Med.

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Background: Atrial fibrillation (AF) is the most common tachyarrhythmia around the world. Cancer is one of the main causes of death worldwide. A recent study demonstrated that cancer was associated with an increased incidence of AF. In the present study, we aimed to explore possible mechanisms and potential common therapeutic targets between AF and cancer.Methods: Differentially expressed proteins between AF and sinus rhythm were identified utilizing proteomics analysis. Weighted gene correlation network analysis was applied to cluster proteins into different modules and investigate associations between modules and AF. Hub immune-related genes were selected via InnateDB database and verified using qRT-PCR. RNA sequencing and clinical data of 33 different cancer types were achieved from The Cancer Genome Atlas (TCGA). The correlations between ANXA4 expression and the prognosis were calculated utilizing Cox regression analysis and Kaplan-Meier survival analysis. Spearman's rank correlation test was used to assess associations between ANXA4 and immune infiltration and DNA methylation. Enrichment analysis was performed through gene ontology and gene set enrichment analysis (GSEA).Results:ANXA4 was identified as hub immune-related gene between AF and sinus rhythm. Expression levels of ANXA4 increased in diverse cancer types. Survival analysis suggested prognostic significance of ANXA4 expression levels in various cancer types. Immune correlation analysis indicated that ANXA4 expression levels were associated with tumor immune infiltration in most cancer types. ANXA4 might influence the efficacy of immunotherapy via tumor burden and microsatellite instability. GSEA results indicated that high ANXA4 expression groups were mainly enriched in peroxisome, bile acid biosynthesis, and p53 pathway.Conclusion:ANXA4 was identified as a hub immune-related gene in AF, which has never been reported. Pan-cancer analysis indicated its potential as a novel clinical prognostic marker and therapeutic target in diverse cancer types. ANXA4 might play crucial roles in AF and cancer, and targeted therapy for ANXA4 might reduce the incidence of AF in cancer patients.

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“…However, AFP-L3 has not been recognized as a conventional diagnostic indicator of HCC. Saad et al reported in HCV-related HCC patients (n=30) that serum levels of annexin A4 (ANXA4) might be a promising biomarker for the early diagnosis of HCC [40].…”

Section: Clinical and Biochemical Markersmentioning

confidence: 99%

Incidence, Diagnosis, and Management of Hepatocellular Carcinoma: Current Perspectives and Future Direction

2023

J Dig Dis Hepatol

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Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, and due to substantial morbidity and mortality, has proven a significant global health-economic burden. Treatment options are broad and include surgical approaches (i.e., transplantation and resection), radiological (i.e., percutaneous ablation, and trans arterial approaches) and systemic therapies, though treatment response often remains poor. As such, clinical decision making requires a multidisciplinary approach to improve treatment strategy after consideration of the patient's tumor stage, liver function, and performance status. Current systemic cytotoxic therapies for non-surgical candidates have largely remained unchanged over the last decade. Systemic therapies have extended life expectancy by up to 3 months but not without potential notable adverse effects that often limit their use. However, even if patients have necessary access to best treatment, survival outcomes remain concerningly poor. Improved understanding of the pathogenic role of advanced liver fibrosis and wider cancer biology is spearheading the development of targeted immunogenic therapies that appear to offer real promise. Importantly, limiting progression to cirrhosis and early detection of HCC in at risk groups, alongside best use of currently accessible therapeutic options, remains key across global healthcare systems. The focus of this review is to critically assess all current published literature, encapsulating the prevalence, diagnosis, and management of HCC, whilst looking ahead to the potential future therapeutic directions in HCC management.

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Clinical Significance of Annexin A4 as a Biomarker in the Early Diagnosis of Hepatocellular Carcinoma

Cited by 8 publications

References 19 publications

Fecal Proteome Profile in Dogs Suffering from Different Hepatobiliary Disorders and Comparison with Controls

Fecal Proteome Profile in Dogs Suffering from Different Hepatobiliary Disorders and Comparison with Controls

Pan-Cancer Analysis of Atrial-Fibrillation-Related Innate Immunity Gene ANXA4

Incidence, Diagnosis, and Management of Hepatocellular Carcinoma: Current Perspectives and Future Direction

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