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Dabbish AM, Abdelzaher HM, Abohawya M, Shamma S, Mahmoud YH, Maged A, Manaa M, Hassany M, Kobeissy F, Bazgir O, El-Fawal H, Azzazy HME, Abdelnaser A. Prognostic MicroRNA Panel for HCV-Associated HCC: Integrating Computational Biology and Clinical Validation. Cancers (Basel) 2022; 14:3036. [PMID: 35804809 PMCID: PMC9265118 DOI: 10.3390/cancers14133036] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Revised: 01/29/2022] [Accepted: 02/05/2022] [Indexed: 02/06/2023] Open
Abstract
Early detection of hepatocellular carcinoma (HCC) will reduce morbidity and mortality rates of this widely spread disease. Dysregulation in microRNA (miRNA) expression is associated with HCC progression. The objective is to identify a panel of differentially expressed miRNAs (DE-miRNAs) to enhance HCC early prediction in hepatitis C virus (HCV) infected patients. Candidate miRNAs were selected using a bioinformatic analysis of microarray and RNA-sequencing datasets, resulting in nine DE-miRNAs (miR-142, miR-150, miR-183, miR-199a, miR-215, miR-217, miR-224, miR-424, and miR-3607). Their expressions were validated in the serum of 44 healthy individuals, 62 non-cirrhotic HCV patients, 67 cirrhotic-HCV, and 72 HCV-associated-HCC patients using real-time PCR (qPCR). There was a significant increase in serum concentrations of the nine-candidate miRNAs in HCC and HCV patients relative to healthy individuals. MiR-424, miR-199a, miR-142, and miR-224 expressions were significantly altered in HCC compared to non-cirrhotic patients. A panel of five miRNAs improved sensitivity and specificity of HCC detection to 100% and 95.12% relative to healthy controls. Distinguishing HCC from HCV-treated patients was achieved by 70.8% sensitivity and 61.9% specificity using the combined panel, compared to alpha-fetoprotein (51.4% sensitivity and 60.67% specificity). These preliminary data show that the novel miRNAs panel (miR-150, miR-199a, miR-224, miR-424, and miR-3607) could serve as a potential non-invasive biomarker for HCC early prediction in chronic HCV patients. Further prospective studies on a larger cohort of patients should be conducted to assess the potential prognostic ability of the miRNAs panel.
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Affiliation(s)
- Areeg M. Dabbish
- Biotechnology Graduate Program, Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt; (A.M.D.); (M.A.)
| | - Hana M. Abdelzaher
- Institute of Global Health and Human Ecology (IGHHE), The American University in Cairo, New Cairo 11835, Egypt; (H.M.A.); (S.S.); (H.E.-F.)
| | - Moustafa Abohawya
- Biotechnology Graduate Program, Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo 11835, Egypt; (A.M.D.); (M.A.)
| | - Samir Shamma
- Institute of Global Health and Human Ecology (IGHHE), The American University in Cairo, New Cairo 11835, Egypt; (H.M.A.); (S.S.); (H.E.-F.)
| | - Yosra H. Mahmoud
- Fellow of Clinical Pathology, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo 11562, Egypt;
| | - Amr Maged
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo 11562, Egypt; (A.M.); (M.M.); (M.H.)
| | - Mohamed Manaa
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo 11562, Egypt; (A.M.); (M.M.); (M.H.)
| | - Mohamed Hassany
- Tropical Medicine Department, National Hepatology and Tropical Medicine Research Institute (NHTMRI), Cairo 11562, Egypt; (A.M.); (M.M.); (M.H.)
| | - Firas Kobeissy
- Program for Neurotrauma, Neuroproteomics & Biomarkers Research, Departments of Emergency Medicine, Psychiatry, Neuroscience and Chemistry, University of Florida, Gainesville, FL 32611, USA;
- Department of Biochemistry and Molecular Biology, American University of Beirut, Beirut 11-0236, Lebanon
| | - Omid Bazgir
- Modeling and Simulation/Clinical Pharmacology, Genentech, CA 94080, USA;
| | - Hassan El-Fawal
- Institute of Global Health and Human Ecology (IGHHE), The American University in Cairo, New Cairo 11835, Egypt; (H.M.A.); (S.S.); (H.E.-F.)
| | - Hassan M. E. Azzazy
- Department of Chemistry, The American University in Cairo, New Cairo 11835, Egypt;
| | - Anwar Abdelnaser
- Institute of Global Health and Human Ecology (IGHHE), The American University in Cairo, New Cairo 11835, Egypt; (H.M.A.); (S.S.); (H.E.-F.)
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In vivo Study of a Newly Synthesized Chromen-4-one Derivative as an Antitumor Agent against HCC. J Gastrointest Cancer 2021; 53:980-989. [PMID: 34698995 DOI: 10.1007/s12029-021-00724-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/26/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Chromenes are a wide group of natural compounds that can be synthesized chemically. The chromen-4-one nucleus acts as a skeleton for varieties of additional active groups that makes the chromene activity vary between antioxidant and anti-inflammatory agents. In the present study, a newly synthesized chromene compound exhibits different behaviors other than anti-inflammatory and antioxidant activities that it is the first time that a member of chromen-4-one compound can control the cancer progress. Inflammation is the first step in tumor development where the severity grade can potentiate tumor growth and progression. In many tumors, pro-inflammatory genes record high expression level such as tumor necrosis factor (TNF-α) and vascular endothelial growth factors (VEGF). These pro-inflammatory factors act as rate limiting steps in tumor initiation, and controlling its expression acts as an early therapeutic way to control the tumor proliferation. The chromone derivatives have biological activities such as anti-inflammatory and anti-tumor activity. METHODS In the present study, hepatocellular cancer (HCC) induced by diethylnitrosamine (DEN) in rats and then treated with the new chromene derivative and the parameters TNF-α, VEGF, p53, Cyt C, MMP-9, Bcl2, and Bax were measured. RESULTS The treatment strategy Ch compound is to downregulate pro-inflammatory gene expression of early genes as TNF-α as well as VEGF and subsequently control other factors such as p53, Cyt C, and MMP-9. Also, retrieve the balance between Bcl2 and Bax proteins in DEN-induced HCC in rats. CONCLUSION The ability of the new Ch derivative to control the primary initiators of HCC such as TNF-α offers this derivative an anti-tumor activity and encourages further researches to follow and monitor its effect on the molecular level.
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Abd-Elfattah ME, Naguib M, Elkheer M, Abdelsameea E, Nada A. The role of IL-4 gene polymorphism in HCV-related hepatocellular carcinoma in Egyptian patients. EGYPTIAN LIVER JOURNAL 2021. [DOI: 10.1186/s43066-021-00081-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Abstract
Background
Interleukin-4 (IL-4), a pleiotropic anti-inflammatory cytokine, is produced mainly by activated T helper 2 (Th2). Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer. Alterations influencing IL-4 expression may disturb immune response and may be associated with HCC risk. We aimed to verify role of IL4 gene polymorphism (IL-4-589C/T (rs2243250)) in HCV-related hepatocellular carcinoma in Egyptian patients. IL-4-589C/T (rs2243250) polymorphism was examined in 50 patients with HCC on top of HCV, 40 patients with HCV-induced liver cirrhosis, and 30 healthy controls using the polymerase chain reaction- restriction fragment length polymorphism method.
Results
Overall IL-4 gene polymorphism (IL-4-589C/T (rs2243250)) showed significant difference between hepatocellular carcinoma group versus liver cirrhosis and healthy control groups. TT homozygous genotype was more prevalent in HCC group (24%) versus (5%) in liver cirrhosis and (3.3%) in control. TT homozygous genotype had 10 times more risk of hepatocellular carcinoma versus healthy control group and 6.33 times more risk versus cirrhotic patients group (p value = 0.018 and 0.016 respectively).
Conclusion
IL-4-589C/T (rs2243250) polymorphism, TT homozygous genetic model, may be a risk factor in HCV-related HCC in Egyptian patients.
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Aboul Enein AA, Khaled IAA, Khorshied MM, Abdel-Aziz AO, Zahran N, El Saeed AM, Shousha HI, Abdel Rahman HA. Genetic variations in DNA-repair genes (XRCC1, 3, and 7) and the susceptibility to hepatocellular carcinoma in a cohort of Egyptians. J Med Virol 2020; 92:3609-3616. [PMID: 32281666 DOI: 10.1002/jmv.25873] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Revised: 03/26/2020] [Accepted: 03/27/2020] [Indexed: 01/01/2023]
Abstract
Chronic hepatitis C (CHC) is a worldwide etiology of chronic hepatic insult particularly in Egypt. DNA-repair systems are responsible for maintaining genomic integrity by countering threats posed by DNA lesions. Deficiency in the repair capacity due to genetic alterations in DNA-repair genes can lead to genomic instability and increased risk of cancer development. The present work aimed at studying the possible association between XRCC1-G28152A (rs25487), XRCC3-C18067T (rs861539), and XRCC7-G6721T (rs7003908) single nucleotide polymorphisms (SNPs) and the susceptibility to hepatocellular carcinoma (HCC) in Egyptian population. The study was conducted on 100 newly diagnosed HCC patients and 100 age- and sex-matched healthy controls. Laboratory workup revealed that all HCC patients have chronic hepatitis C viral infection. Genotyping of the studied SNPs was performed by real-time PCR. The heteromutant genotype of XRCC1 (GA) conferred an almost two-fold increased risk of HCC (OR , 2.35; 95% CI, 1.33-4.04). Regarding XRCC7, the heteromutant (TG) genotype conferred a two-fold increased risk of HCC (OR , 2.17; 95% CI, 1.23-3.82). Coinheritance of the polymorphic genotypes of XRCC1 and 7 was significantly higher in HCC cases than controls and was associated with an 11-fold increased risk of HCC (OR , 11.66; 95% CI, 2.77-49.13). The frequency of XRCC3 polymorphic genotypes in HCC patients was close to that of the controls.
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Affiliation(s)
- Azza Ahmed Aboul Enein
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Iman Abdel Aziz Khaled
- Department of Clinical and Chemical Pathology, Theoder Bilharz Research Institute, Cairo, Egypt
| | - Mervat Mamdooh Khorshied
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | | | - Nariman Zahran
- Department of Clinical and Chemical Pathology, Theoder Bilharz Research Institute, Cairo, Egypt
| | - Asmaa Mohamed El Saeed
- Department of Clinical and Chemical Pathology, Theoder Bilharz Research Institute, Cairo, Egypt
| | - Hend Ibrahim Shousha
- Department of Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hala Aly Abdel Rahman
- Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt
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Mamdouh F, Abdel Alem S, Abdo M, Abdelaal A, Salem A, Rabiee A, Elsisi O. Serum Serotonin as a Potential Diagnostic Marker for Hepatocellular Carcinoma. J Interferon Cytokine Res 2019; 39:780-785. [PMID: 31478787 DOI: 10.1089/jir.2019.0088] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
To assess the potential role of serum serotonin level in hepatocellular carcinoma (HCC) diagnosis. A case-control study that involved 100 Egyptian adults. Subjects were divided into 4 groups: Group I: 21 patients with late-stage HCC on top of liver cirrhosis, Group II: 28 patients with early-stage HCC on top of liver cirrhosis, Group III: 26 patients with cirrhosis with no evidence of HCC, and Group IV: 25 healthy age- and sex-matched subjects were as a control group. Serum serotonin level was determined in all recruited subjects using high-performance liquid chromatography-fluorescent detection method. Alpha-fetoprotein had a statistically significant elevation in group I with a median of 1300 ng/L (195-2544 ng/L) compared to groups II and III (P ≤ 0.01). Regarding serum serotonin level, it had a statistically significant elevation in group II with a median of 275 ng/μL (204.7-400 ng/μL) compared to groups I, III, and IV with median of 33 ng/μL (30-50 ng/μL), 50 ng/μL (30-60 ng/μL), and 102 (85-150 ng/μL), respectively (P = 0.001). Receiver operating characteristic curve showed that serum serotonin at cutoff value of 108 ng/μL had a sensitivity of 100% and specificity of 92.3% in discriminating early-stage HCC from cirrhosis. Serum serotonin level is a rapid, sensitive, noninvasive diagnostic biomarker for the detection of early-stage HCC.
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Affiliation(s)
- Fatma Mamdouh
- Clinical and Chemical Pathology Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
| | - Shereen Abdel Alem
- Endemic Medicine and Hepatology Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
| | - Mahmoud Abdo
- Endemic Medicine and Hepatology Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
| | - Amaal Abdelaal
- Clinical and Chemical Pathology Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
| | - Amel Salem
- Internal Medicine Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Rabiee
- Internal Medicine Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
| | - Ola Elsisi
- Clinical and Chemical Pathology Department, Kasr Alaini School of Medicine, Cairo University, Cairo, Egypt
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Abd El Moety HA, Maharem DA, Gomaa SH. Serotonin: is it a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients? ALEXANDRIA JOURNAL OF MEDICINE 2019. [DOI: 10.1016/j.ajme.2013.03.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Hoda Aly Abd El Moety
- Chemical Pathology, Medical Research Institute , Alexandria University , 16 Alexander the Great , Azarita, Alexandria, Egypt
| | - Dalia Aly Maharem
- Internal Medicine, Medical Research Institute , Alexandria University , 16 Alexander the Great , Azarita, Alexandria, Egypt
| | - Salwa Hamdy Gomaa
- Chemical Pathology, Medical Research Institute , Alexandria University , 16 Alexander the Great , Azarita, Alexandria, Egypt
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Hepatitis C virus and schistosomiasis as a causative factor for hTERT amplification in hepatocellular carcinoma. GENE REPORTS 2016. [DOI: 10.1016/j.genrep.2016.09.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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Elsayed HM, Nabiel Y, Sheta T. IL12 Gene Polymorphism in Association with Hepatocellular Carcinoma in HCV-infected Egyptian Patients. Immunol Invest 2016; 46:123-133. [DOI: 10.1080/08820139.2016.1229789] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Heba Mosaad Elsayed
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Yasmin Nabiel
- Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Tarek Sheta
- Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
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Could serotonin be a potential marker for hepatocellular carcinoma? A prospective single-center observational study. Eur J Gastroenterol Hepatol 2016; 28:599-605. [PMID: 26741637 DOI: 10.1097/meg.0000000000000569] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, which may be involved in the tumorigenesis of HCC. AIM We aimed to determine whether serotonin is a dependable marker for the diagnosis of HCC in cirrhotic patients in comparison with α-fetoprotein protein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II). PATIENTS AND METHODS Serum serotonin, AFP, and PIVKA-II were measured in 262 patients with chronic hepatitis C (CHC): 82 cirrhotic patients with HCC (group I), 80 cirrhotic patients without HCC (group II), and 100 CHC-infected patients without cirrhosis (group III); in addition, 60 healthy controls were studied (group IV). RESULTS AFP showed significant statistical differences among the groups studied (P<0.001). PIVKA-II and serotonin levels showed no statistically significant differences between the patients with CHC group and the healthy controls (P1=0.614 and P1=0.13, respectively), whereas their levels were statistically higher in cirrhotic patients than patients with CHC (all P values <0.001) and in the cirrhotic patients with HCC group than the cirrhotic patients without HCC (P<0.001). A significant positive correlation was found between serum serotonin and AFP (rho=0.794; P<0.001) and serum serotonin and PIVKA-II (rho=0.889; P<0.001) among the patient groups. The receiver operator characteristic curve showed a higher area under the curve for serotonin than AFP and PIVKA-II (0.942, 0.824, and 0.921, respectively). CONCLUSION Serotonin may be used together with PIVKA-II to screen for HCC in cirrhotic patients with CHC.
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Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective. J Parasit Dis 2014; 40:976-80. [PMID: 27605822 DOI: 10.1007/s12639-014-0618-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Accepted: 11/11/2014] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It was reported to account for about 4.7 % of chronic liver disease in Egyptian patients. The present study aimed at studying the different factors that may be implicated in the relationship of schistosomiasis mansoni with HCC in Egypt. A total of 75 Egyptian patients with primary liver tumours (HCC) were enrolled in this study. They were subjected to full history taking and indirect hemagglutination assay (IHA) for the diagnosis of schistosomiasis. According to the results, the patients were categorized into two groups: Group I: 29 patients with negative IHA for schistosomiasis and hepatitis C virus (HCV) positive with no history or laboratory evidence of previous or current Schistosoma mansoni infection. Group II: 46 patients with positive IHA for schistosomiasis and HCV positive. The significant higher proportion of HCC patients in the present study had concomitant HCV and schistosomiasis (61.3 %) compared to HCC patients with HCV alone (38.7 %) suggesting that the co-infection had increased the incidence of HCC among these patients. Analysis of the age distribution among HCC patients revealed that patients in Group II were younger in age at time of diagnosis of HCC with mean age 57.1 years, as compared to patients in Group I with mean age 64.3 years with a highly significant statistical difference between the 2 groups. HCC in Group II was more common in rural residents while it was more common in urban areas in Group I with a significant statistical difference between the 2 groups. Analysis of the sex distribution among the studied groups showed that HCC was more common in males than females in both groups. As regards the aggression of HCC, it was more commonly multifocal and larger in size in patients with concomitant infection than in patients with HCV alone.
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El-Garem H, Ammer A, Shehab H, Shaker O, Anwer M, El-Akel W, Omar H. Circulating microRNA, miR-122 and miR-221 signature in Egyptian patients with chronic hepatitis C related hepatocellular carcinoma. World J Hepatol 2014; 6:818-824. [PMID: 25429320 PMCID: PMC4243156 DOI: 10.4254/wjh.v6.i11.818] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Revised: 08/20/2014] [Accepted: 10/27/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To explore the potential usefulness of serum miR-122 and miR-221 as non-invasive diagnostic markers of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC).
METHODS: This prospective study was conducted on 90 adult patients of both sex with HCV-related chronic liver disease and chronic hepatitis C related HCC. In addition to the 10 healthy control individuals, patients were stratified into; interferon-naïve chronic hepatitis C (CH) (n = 30), post-hepatitis C compensated cirrhosis (LC) (n = 30) and treatment-naïve HCC (n = 30). All patients and controls underwent full clinical assessment and laboratory investigations in addition to the evaluation of the level of serum miRNA expression by RT-PCR.
RESULTS: There was a significant fold change in serum miRNA expression in the different patient groups when compared to normal controls; miR-122 showed significant fold increasing in both CH and HCC and significant fold decrease in LC. On the other hand, miR-221 showed significant fold elevation in both CH and LC groups and significant fold decrease in HCC group (P = 0.01). Comparing fold changes in miRNAs in HCC group vs non HCC group (CH and Cirrhosis), there was non-significant fold elevation in miR-122 (P = 0.21) and significant fold decreasing in miR-221 in HCC vs non-HCC (P = 0.03). ROC curve analysis for miR-221 yielded 87% sensitivity and 40% specificity for the differentiation of HCC patients from non-HCC at a cutoff 1.82.
CONCLUSION: Serum miR-221 has a strong potential to serve as one of the novel non-invasive biomarkers of HCC.
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Ahmed HH, Khalil WKB, Hamza AH. Molecular mechanisms of Nano-selenium in mitigating hepatocellular carcinoma induced byN-nitrosodiethylamine (NDEA) in rats. Toxicol Mech Methods 2014; 24:593-602. [DOI: 10.3109/15376516.2014.956912] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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13
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Impact of PIVKA-II in diagnosis of hepatocellular carcinoma. J Adv Res 2013; 4:539-46. [PMID: 25685463 PMCID: PMC4294786 DOI: 10.1016/j.jare.2012.10.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Revised: 10/22/2012] [Accepted: 10/28/2012] [Indexed: 12/22/2022] Open
Abstract
Liver cancer grows silently with mild or no symptoms until advanced. In the absence of an effective treatment for advanced stage of hepatic cancer hope lies in early detection, and screening for high-risk population. Among Egyptians viral hepatitis is the most common risk factor for hepatocellular carcinoma (HCC). The current work was designed to determine the level of prothrombin induced by vitamin K absence-II (PIVKA-II) in sera of patients suffering from HCC and hepatitis C virus (HCV) patients being the most common predisposing factor for HCC. Our ultimate goal is diagnosis of HCC at its early stage. The current study was carried out on 83 individuals within three groups; Normal control, HCV and HCC groups. Patients were subdivided into cirrhotic and non-cirrhotic. Complete clinicopathological examination was carried out for each individual to confirm diagnosis. Individuals’ sera were subjected to quantitative determination of alpha-fetoprotein (AFP), PIVKA-II and other parameters. PIVKA-II proved to be superior to AFP for early detection of HCC patients being highly sensitive and specific. Furthermore it has the ability to discriminate between different histopathological grades of HCC and It has a powerful diagnostic validity to evaluate the thrombosis of portal vein and to differentiate between early and late stages of HCC. The direct relation between the level of PIVKA-II and the size of tumor makes it an attractive tool for early HCC diagnosis and surveillance. Using the best cut-off value of AFP (>28), showed a sensitivity of (44%) and specificity of (73.3%). While cut-off value of PIVKA-II (>53.7) showed 100% sensitivity and specificity.
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Zakhary NI, El-Merzabani MM, El-Sawi NM, Saleh SM, Moneer MM, Mohamad RH. Impact of different biochemical markers in serum of patients with benign and malignant liver diseases. J Adv Res 2011. [DOI: 10.1016/j.jare.2010.08.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
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15
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Berzsenyi MD, Roberts SK, Beard MR. Genomics of Hepatitis B and C Infections: Diagnostic and Therapeutic Applications of Microarray Profiling. Antivir Ther 2006. [DOI: 10.1177/135965350601100515] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Microarray profiling offers many potential advances in diagnostic and therapeutic intervention in human disease because of its unparalleled ability to conduct high-throughput analysis of gene expression. However, limitations of this technique relate in part to issues regarding the various methodologies and experimental designs as well as difficulties in the interpretation of results. Despite this, microarray profiling has led to a better understanding of the molecular pathogenesis of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Key events in clearance and the development of chronicity of HCV have been identified that may prove to have a role in the development of future treatments. In addition, pharmacogenomic studies of interferon-based treatment for chronic HCV and HBV have provided mechanistic insights into the therapeutic action of interferons. These advances have implications with respect to the development of improved therapeutic agents. New biomarkers for cancer screening and gene profiles with prognostic value for survival have also been developed for hepatocellular carcinoma, which frequently complicates chronic viral hepatitis. Thus, microarray profiling offers enormous potential for improvements in antiviral therapy and our understanding of blood-borne viral hepatitis.
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Affiliation(s)
- Mark D Berzsenyi
- Department of Gastroenterology, Alfred Hospital, Victoria, Australia
| | - Stuart K Roberts
- Department of Gastroenterology, Alfred Hospital, Victoria, Australia
| | - Michael R Beard
- Infectious Diseases Laboratories and Hanson Institute, Institute of Medical and Veterinary Science, Adelaide, South Australia
- School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia
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Loilome W, Yongvanit P, Wongkham C, Tepsiri N, Sripa B, Sithithaworn P, Hanai S, Miwa M. Altered gene expression in Opisthorchis viverrini-associated cholangiocarcinoma in hamster model. Mol Carcinog 2006; 45:279-87. [PMID: 16550611 DOI: 10.1002/mc.20094] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cholangiocarcinoma (CCA) induced by liver fluke (Opisthorchis viverrini, Ov) infection is one of the most common and serious disease in northeast Thailand. To elucidate the molecular mechanism of cholangiocarcinogenesis induced by Ov infection, we employed a hamster model of CCA induced by Ov and N-nitrosodimethylamine and analyzed candidate genes involved in CCA using fluorescence differential display-PCR. Of 149 differentially amplified bands we identified, the upregulation of 23 transcripts and downregulation of 1 transcript related to CCA hamsters were confirmed by a reverse northern macroarray blot. The upregulated genes include signal transduction protein kinase A regulatory subunit Ialpha (Prkar1a), myristoylated alanine-rich protein kinase C substrate, transcriptional factor LIM-4-only domain, oxysterol-binding protein involved in lipid metabolism, splicing regulatory protein 9, ubiquitin conjugating enzyme involved in protein degradation, beta tubulin, beta actin, and collagen type VI. Quantitative real-time PCR confirmed that the expression of Prkar1a was significantly higher in CCA and its precursor lesion when compared with normal liver and normal gall bladder epithelia (P<0.05). Prkar1a expression tended to increase along with the progression of biliary transformation from hyperplasia and precancerous lesions to carcinoma. These findings contribute to our understanding of the processes involved in the molecular carcinogenesis of CCA in order to provide a unique perspective on the development of new chemotherapeutics in future.
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Affiliation(s)
- Watcharin Loilome
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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Blanc JF, Lalanne C, Plomion C, Schmitter JM, Bathany K, Gion JM, Bioulac-Sage P, Balabaud C, Bonneu M, Rosenbaum J. Proteomic analysis of differentially expressed proteins in hepatocellular carcinoma developed in patients with chronic viral hepatitis C. Proteomics 2006; 5:3778-89. [PMID: 16097030 DOI: 10.1002/pmic.200401194] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Hepatocellular carcinoma (HCC) is a major complication of chronic viral hepatitis C. Therapy for HCC is still disappointing. It is thus of great importance to identify novel HCC markers for early detection of the disease, and tumor-specific proteins as potential therapeutic targets. We have used a proteomic approach to identify new proteins involved in HCC development. Four cases of HCC developing from chronic viral hepatitis C were analyzed by two-dimensional electrophoresis (2-DE), and results were compared to those of paired adjacent non-tumorous liver tissues. For MS fingerprinting, protein spots with differential intensity between HCC and non-tumorous liver were directly cut out of gels and processed for MALDI-MS and nano-LC-ESI-MS/MS analysis. Approximately 850 spots were visualized in each gel. The comparative analysis of paired samples indicated that 345 protein spots showed significant differences in expression level between non-tumor and tumor tissue. Among the 345 protein spots analyzed, 238 spots corresponding to 155 different proteins were identified; 49 proteins were up-regulated, whereas 106 proteins were down-regulated. Among these 155 proteins, 91 proteins were regulated in at least three cases. Although 52 out of these 91 proteins have been already described by previous proteomic or transcriptomic studies, or are already known to be involved in hepatocarcinogenesis, this experiment revealed 39 new proteins differentially expressed in HCC developing from viral hepatitis C. Variations in protein accumulation were confirmed for two selected proteins (apolipoprotein E, chloride intracellular channel 1) by Western blotting in ten additional cases of HCC developing in patients with viral hepatitis C.
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Affiliation(s)
- Jean-Frédéric Blanc
- INSERM, E362, IFR66 Bordeaux, Université Victor Segalen Bordeaux 2, Bordeaux, France
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Cheng P, Gong J, Wang T, Chen J, Liu GS, Zhang R. Gene expression in rats with Barrett’s esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux. World J Gastroenterol 2005; 11:5117-22. [PMID: 16127739 PMCID: PMC4320382 DOI: 10.3748/wjg.v11.i33.5117] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the different gene expression profiles in rats with Barrett’s esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodeno-esophageal reflux.
METHODS: Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodeno-esophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4 096 genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray.
RESULTS: Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255 upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltra-nsferase, lysozyme, complement 4b binding protein, complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand.
CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.
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Affiliation(s)
- Peng Cheng
- Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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Cheng P, Gong J, Wang T, Chen J, Liu GS, Zhang R. Gene expression in rats with Barrett's esophagus and esophageal adenocarcinoma induced by gastroduodenoesophageal reflux. World J Gastroenterol 2005. [PMID: 16127739 DOI: 10.3748/wjg.v11.i21.5117] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To study the different gene expression profiles in rats with Barrett's esophagus (BE) and esophageal adenocarcinoma (EA) induced by gastro-duodeno-esophageal reflux. METHODS Esophagoduodenostomy was performed in 8-wk old Sprague-Dawley rats to induce gastro-duodeno-esophageal reflux, and a group of rats that received sham operation served as control. Esophageal epithelial pathological tissues were dissected and frozen in liquid nitrogen immediately. The expression profiles of 4096 genes in EA and BE tissues were compared to normal esophagus epithelium in normal control (NC) by cDNA microarray. RESULTS Four hundred and forty-eight genes in BE were more than three times different from those in NC, including 312 upregulated and 136 downregulated genes. Three hundred and seventy-seven genes in EA were more than three times different from those in NC, including 255 upregulated and 142 downregulated genes. Compared to BE, there were 122 upregulated and 156 downregulated genes in EA. In the present study, the interested genes were those involved in carcinogenesis. Among them, the upregulated genes included cathepsin C, aminopeptidase M, arachidonic acid epoxygenase, tryptophan-2,3-dioxygenase, ubiquitin-conjugating enzyme, cyclic GMP-stimulated phosphodiesterase, tissue inhibitor of metalloproteinase-1, betaine-homocysteine methyltransferase, lysozyme, complement 4b binding protein, complement 9 protein, insulin-like growth factor binding protein, UDP-glucuronosyltransferase, tissue inhibitor of metalloproteinase-3, aldolase B, retinoid X receptor gamma, carboxylesterase and testicular cell adhesion molecule 1. The downregulated genes included glutathione synthetase, lecithin-cholesterol acyltransferase, p55CDC, heart fatty acid binding protein, cell adhesion regulator and endothelial cell selectin ligand. CONCLUSION Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux may develop into BE and even EA gradually. The gene expression level is different between EA and BE, and may be related to the occurrence and progression of EA.
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Affiliation(s)
- Peng Cheng
- Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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el-Zayadi AR, Badran HM, Barakat EMF, Attia MED, Shawky S, Mohamed MK, Selim O, Saeid A. Hepatocellular carcinoma in Egypt: A single center study over a decade. World J Gastroenterol 2005; 11:5193-8. [PMID: 16127751 PMCID: PMC4320394 DOI: 10.3748/wjg.v11.i33.5193] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify the trend, possible risk factors and any pattern change of hepatocellular carcinoma (HCC) in Egypt over a decade.
METHODS: All HCC patients attending Cairo Liver Center between January 1993 and December 2002, were enrolled in the study. Diagnosis of HCC was based on histopathological examination and/or detection of hepatic focal lesions by two imaging techniques plus α-fetoprotein level above 200 ng/mL. The duration of the study was divided into two periods of 5 years each; period I (1993-1997) and period II (1998-2002). Trend, demographic features of patients (age, gender, and residence), risk factors (HBsAg, HCV-Ab, schistosomiasis and others) and pattern of the focal lesions were compared between the two periods. Logistic regression model was fitted to calculate the adjusted odds ratios for the potential risk factors. The population attributable risk percentage was calculated to estimate the proportion of HCC attributed to hepatitis B and C viral infections.
RESULTS: Over a decade, 1 328 HCC patients out of 22 450 chronic liver disease (CLD) patients were diagnosed with an overall proportion of 5.9%. The annual proportion of HCC showed a significant rising trend from 4.0% in 1993 to 7.2% in 2002 (P = 0.000). A significant increase in male proportion from 82.5% to 87.6% (P = 0.009); M/F from 5:1 to 7:1 and a slight increase of the predominant age group (40-59 years) from 62.6% to 66.8% (P = 0.387) in periods I and II respectively, reflecting a shift to younger age group. In the bivariate analysis, HCC was significantly higher in rural residents, patients with history of schistoso-miasis and/or blood transfusion. Yet, after adjustment, these variables did not have a significant risk for development of HCC. There was a significant decline of HBsAg from 38.6% to 20.5% (P = 0.000), and a slight increase of HCV-Ab from 85.6% to 87.9% in periods I and II respectively. HBV conferred a higher risk to develop HCC more than HCV in period I (OR 1.9 vs 1.6) and period II (OR 2.7 vs 2.0), but the relative contribution of HBV for development of HCC declined in period II compared to period I (PAR% 4.2%, 21.32%). At presentation, diagnostic α-fetoprotein level (≥200 ng/mL) was demonstrated in 15.6% vs 28.9% and small HCC (≤3 cm) represented 14.9% vs 22.7% (P = 0.0002) in periods I and II respectively.
CONCLUSION: Over a decade, there was nearly a twofold increase of the proportion of HCC among CLD patients in Egypt with a significant decline of HBV and slight increase of HCV as risk factors. α-Fetoprotein played a limited role in diagnosis of HCC, compared to imaging techniques. Increased detection of small lesions at presentation reflects increased awareness of the condition.
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Cheng P, Gong J, Wang T, Jie C, Liu GS, Zhang R. Gene expression in Barrett’s esophagus and reflux esophagitis induced by gastroduodenoesophageal reflux in rats. World J Gastroenterol 2005; 11:3277-80. [PMID: 15929182 PMCID: PMC4316063 DOI: 10.3748/wjg.v11.i21.3277] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the difference of gene expression profiles between Barrett’s esophagus and reflux eso-phagitis induced by gastroduodenoesophageal reflux in rats.
METHODS: Eight-week-old Sprague-Dawley rats were treated esophagoduodenostomy to produce gastroduode-noesophageal reflux, and another group received sham operation as control. Esophageal epithelial tissues were dissected and frozen in liquid nitrogen immediately for pathology 40 wk after surgery. The expression profiles of 4096 genes in reflux esophagitis and Barrett’s esophagus tissues were compared with normal esophageal epithelium by cDNA microarray.
RESULTS: Four hundred and forty-eight genes in Barrett’s esophagus were more than three times different from those in normal esophageal epithelium, including 312 up-regulated and 136 down-regulated genes. Two hundred and thirty-two genes in RE were more than three times different from those in normal esophageal epithelium, 90 up-regulated and 142 down-regulated genes. Compared to reflux esophagitis, there were 214 up-regulated and 142 down-regulated genes in Barrett’s esophagus.
CONCLUSION: Esophageal epithelium exposed excessively to harmful ingredients of duodenal and gastric reflux can develop esophagitis and Barrett’s esophagus gradually. The gene expression level is different between reflux esophagitis and Barrett’s esophagus and the differentially expressed genes might be related to the occurrence and development of Barrett’s esophagus and the promotion or progression in adenocarcinoma.
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Affiliation(s)
- Peng Cheng
- Department of Gastroenterology, Second Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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