Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection

Bird, Thomas; Dimitropoulou, Polyxeni; Turner, Rebecca; Jenks, Sara; Cusack, Pearce; Hey, Shi Ying; Blunsum, Andrew; Kelly, Sarah L.; Sturgeon, Catharine M.; Hayes, Peter; Bird, Sheila M.

doi:10.1371/journal.pone.0156801

Cited by 34 publications

(32 citation statements)

References 38 publications

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“…This role is in line with a number of recent reports proposing a rationale for the ongoing use of AFP to identify and follow patients at higher risk of HCC (74)(75)(76).…”

Section: Disclosuresupporting

confidence: 75%

Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

Toraih

Fawzy

El-Falouji

et al. 2016

Mol Med

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and 6 Pulmonologist, Ministry of Health, EgyptStem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profiles of three pluripotency-associated genes, OCT4, NANOG and SOX2, G-protein-coupled chemokine receptor 4 (CXCR4) and the ligand CXCL2, and alpha-fetoprotein (AFP) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed for relative quantification of the six target genes using the Livak method. In silico network analysis was also executed to explore the pluripotency and tumorigenetic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG, CXCR4 and AFP were significantly upregulated in late clinical stage HCC patients. In contrast, SOX2 and CXCL2 were markedly overexpressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of the SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high expression with late HCC could contribute to the acquisition of stem celllike properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have potential application in HCC prognosis and treatment.

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“…This role is in line with a number of recent reports proposing a rationale for the ongoing use of AFP to identify and follow patients at higher risk of HCC (74)(75)(76).…”

Section: Disclosuresupporting

confidence: 75%

Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

Toraih

Fawzy

El-Falouji

et al. 2016

Mol Med

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“…Interestingly, in addition to our data, a study on patients with pancreatic adenocarcinoma showed increased CA19‐9 values as early as 2‐3 years before diagnosis . A similar observation was reported for changes in serum levels of alpha‐fetoprotein prior to development of hepatocellular carcinoma …”

Section: Resultssupporting

confidence: 90%

Longitudinal analysis of CA19‐9 reveals individualised normal range and early changes before development of biliary tract cancer in patients with primary sclerosing cholangitis

Wannhoff

Brune

Knierim

et al. 2019

Aliment Pharmacol Ther

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Background: Primary sclerosing cholangitis is associated with an increased risk of biliary tract cancer. Carbohydrate antigen 19-9 (CA19-9) can be used to screen for these malignancies.Aim: To perform a longitudinal analysis of CA19-9 in patients with primary sclerosing cholangitis. Methods:We conducted a retrospective analysis of CA19-9 values in patients who had primary sclerosing cholangitis, with and without biliary malignancy. We calculated the index of individuality and reference change value in patients who were

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“…Immunohistochemistry analyze of Pang Li et al show that in HCC patients with low serum AFP levels, immunohistochemistry still exhibited stronger AFPR staining (30). Expression of AFP, although observed in only about one third of the cases, favored HCC over cholangiocellular carcinoma and metastases (31,32). Also the immunochemistry test showed Ki-67 activity in 40%.…”

Section: Discussionmentioning

confidence: 99%

A case of anaplastic liver cancer after HCV eradication with IFN- free therapy

Nikolova¹,

Handzhiev²,

Petrov³

et al. 2018

MedInform

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IntroductionHepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers and is a major global health problem. In the era of Direct acting agents (DAA) for treatment of hepatitis C virus (HCV), sustained virological response (SVR) is achieved in more than 80% of cases. Accumulating clinical experience of DAA-based treatment has suggested that post-SVR HCC development and recurrence may be more frequent compared to interferon (IFN)-based treatment. We describe a case of poor differentiated HCC in non-cirrhotic liver, after HCV-eradication. Case presentation:A 73-year-old female presented with HCV-hepatitis at the beginning of 2017. A liver biopsy showed low grade fibrosis (F1). HCV genotype was 1b, with viral load 680 500 IU/ml. She was anti-HBc total positive, but negative for hepatitis B surface antigen (HBsAg) and HBV DNAnegative, and also anti-HIV 1/2 and had no history of alcohol or drug abuse. In May 2017 -treatment with IFN-free regime was started -3D -Viekirax and Exviera, without Ribavirin. At the 4th week of treatment HCV RNA was negative. At the 12th week abdominal ultrasound (US) showed a 60 mm liver nodule in 6th segment and a few more nodules form 10 to 32 mm. AFP was slightly elevated (59 ng/ml). Original ArticleMedInform I S S U E 2 , 2 0 1 8 MedInformThe contrast enhanced computed tomography (CT) scan showed typical signs of HCC. Ultra sound (US)-guided biopsy was performed. Histological result was: Anaplastic carcinoma with stromal desmoplasia and expressed lymphocyte stromal reaction (a liver origin is possible). Immunohistochemistry test showed: Alpha-feto protein -negative reaction; Ca 19-9 -negative reaction, but Ki67 -40% proliferative activity. The patient was at stage B according to Barcelona-clinic liver cancer (BCLC) classification and treatment with Sorafenib was started. Discussion:Sequence of chronic hepatitis -cirrhosis -HCC is well known. In these cases the major role in oncogenesis is due to severe fibrosis and inflammation. HCC in non-cirrhotic liver is not well understood.The oncogenic potential of core protein of HCV has been discussed and therefore HCV is directly involved in hepatocarcinogenesis. Recent studies show higher frequency of HCC in patients with 1b HCV infection. In presented case -the patient was infected with HCV subgenotype 1b and had very low stage of fibrosis. But she was anti HBcor -positive and after HCV eradication. Several studies suggested a possibly distinct difference in host immune modulation between interferon and DAAs.Because of multiple character of HCC (more than 3 nodule, exactly 7 in this case), the initial treatment was Sorafenib. It was well tolerated and resent CT showed only two nodules. In this stage a RFTA is discussing.

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Alpha-Fetoprotein Detection of Hepatocellular Carcinoma Leads to a Standardized Analysis of Dynamic AFP to Improve Screening Based Detection

Cited by 34 publications

References 38 publications

Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

Stemness-Related Transcriptional Factors and Homing Gene Expression Profiles in Hepatic Differentiation and Cancer

Longitudinal analysis of CA19‐9 reveals individualised normal range and early changes before development of biliary tract cancer in patients with primary sclerosing cholangitis

A case of anaplastic liver cancer after HCV eradication with IFN- free therapy

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