Serum MicroRNA-21 as Marker for Necroinflammation in Hepatitis C Patients with and without Hepatocellular Carcinoma
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{"title"=>"Serum microRNA-21 as marker for necroinflammation in hepatitis C patients with and without hepatocellular carcinoma", "type"=>"journal", "authors"=>[{"first_name"=>"Verena", "last_name"=>"Bihrer", "scopus_author_id"=>"37664405900"}, {"first_name"=>"Oliver", "last_name"=>"Waidmann", "scopus_author_id"=>"6508323887"}, {"first_name"=>"Mireen", "last_name"=>"Friedrich-Rust", "scopus_author_id"=>"15924796800"}, {"first_name"=>"Nicole", "last_name"=>"Forestier", "scopus_author_id"=>"16233099800"}, {"first_name"=>"Simone", "last_name"=>"Susser", "scopus_author_id"=>"24448363600"}, {"first_name"=>"Jörg", "last_name"=>"Haupenthal", "scopus_author_id"=>"9741912100"}, {"first_name"=>"Martin", "last_name"=>"Welker", "scopus_author_id"=>"56276279600"}, {"first_name"=>"Ying", "last_name"=>"Shi", "scopus_author_id"=>"55322223100"}, {"first_name"=>"Jan", "last_name"=>"Peveling-Oberhag", "scopus_author_id"=>"35771536500"}, {"first_name"=>"Andreas", "last_name"=>"Polta", "scopus_author_id"=>"16048176000"}, {"first_name"=>"Michael", "last_name"=>"von Wagner", "scopus_author_id"=>"6602233259"}, {"first_name"=>"Heinfried H.", "last_name"=>"Radeke", "scopus_author_id"=>"7003379958"}, {"first_name"=>"Christoph", "last_name"=>"Sarrazin", "scopus_author_id"=>"7004249751"}, {"first_name"=>"Jörg", "last_name"=>"Trojan", "scopus_author_id"=>"18736761800"}, {"first_name"=>"Stefan", "last_name"=>"Zeuzem", "scopus_author_id"=>"7103125178"}, {"first_name"=>"Bernd", "last_name"=>"Kronenberger", "scopus_author_id"=>"6701811768"}, {"first_name"=>"Albrecht", "last_name"=>"Piiper", "scopus_author_id"=>"7004230496"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"22066022", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0026971", "pui"=>"362837206", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "scopus"=>"2-s2.0-80055103381", "sgr"=>"80055103381"}, "id"=>"840e89ae-d3c5-3cac-91ea-ba2c7f60c5ec", "abstract"=>"BACKGROUND: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = -0.494, P = 0.00002), alanine aminotransferase (ALT) (r = -0.309, P = 0.007), aspartate aminotransferase (r = -0.495, P = 0.000007), bilirubin (r = -0.362, P = 0.002), international normalized ratio (r = -0.338, P = 0.034) and γ-glutamyltransferase (r = -0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dC(T) of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%.\\n\\nCONCLUSIONS/SIGNIFICANCE: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.", "link"=>"http://www.mendeley.com/research/serum-microrna21-marker-necroinflammation-hepatitis-c-patients-without-hepatocellular-carcinoma", "reader_count"=>61, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Student > Doctoral Student"=>5, "Researcher"=>19, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>10, "Other"=>5, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Student > Doctoral Student"=>5, "Researcher"=>19, "Student > Ph. D. Student"=>11, "Student > Postgraduate"=>3, "Student > Master"=>10, "Other"=>5, "Student > Bachelor"=>1, "Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>25, "Agricultural and Biological Sciences"=>22, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Veterinary Science and Veterinary Medicine"=>1, "Chemistry"=>1, "Social Sciences"=>1, "Computer Science"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>25}, "Neuroscience"=>{"Neuroscience"=>1}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>22}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Hong Kong"=>1, "France"=>1, "Germany"=>1, "Russia"=>1, "Spain"=>1}, "group_count"=>2}

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  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/718476/Figure_1.tif"], "description"=>"<p>(A), dC<sub>T</sub> values of miR-21 of sera from healthy control individuals (n = 19), patients with CHC and elevated serum ALT levels (n = 44) and CHC patients with normal serum ALT levels (n = 18). Boxes represent range, median and quartiles of the number of threshold cycles (C<sub>T</sub>) required to detect miR-21 by real-time RT-qPCR normalized to C<sub>T</sub> of miR-16. Differences were calculated with Wilcoxon-Mann-Whitney-U-test. *<i>P</i><.05, ***<i>P</i><.001, compared with the healthy control group. <sup>+++</sup><i>P</i><.001 between CHC patients with normal or elevated ALT. (B), ROC curve analysis of serum miR-21 concentration for discriminating CHC patients and healthy controls. (C), dC<sub>T</sub> values of CHC patients with elevated ALT and HAI≥5 (n = 31) and patients with CHC and HCC (n = 29) showing no significant difference in miR-21 levels (Wilcoxon-Mann-Whitney-U-test: <i>P</i>>.3) between both groups, n. s. = not significant. (D) Relationship between serum miR-21 levels and the serum HCV RNA in patients with CHC. The relation is not significant (<i>P</i> = .29).</p>", "links"=>[], "tags"=>["serum", "mir-21", "concentrations", "patients", "chc", "elevated", "levels"], "article_id"=>388799, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Increased_serum_miR_21_concentrations_in_patients_with_CHC_and_elevated_levels_of_ALT_/388799", "title"=>"Increased serum miR-21 concentrations in patients with CHC and elevated levels of ALT.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:12:29"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/718604/Figure_2.tif"], "description"=>"<p>Relationship between serum miR-21 levels and INR (A), bilirubin (B), γ-GT (C) and serum albumin concentration (D).</p>", "links"=>[], "tags"=>["serum", "mir-21", "levels", "inr", "bilirubin", "albumin"], "article_id"=>388945, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Relationship_between_serum_miR_21_levels_and_INR_A_bilirubin_B_947_GT_C_and_serum_albumin_concentration_D_/388945", "title"=>"Relationship between serum miR-21 levels and INR (A), bilirubin (B), γ-GT (C) and serum albumin concentration (D).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:13:12"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/718756/Figure_3.tif"], "description"=>"<p>Points represent dC<sub>T</sub> values for miR-21 normalized to miR-16.</p>", "links"=>[], "tags"=>["serum", "mir-21", "levels", "alt", "ast", "patients"], "article_id"=>389095, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Correlation_between_serum_miR_21_levels_and_ALT_A_or_AST_B_in_patients_with_CHC_/389095", "title"=>"Correlation between serum miR-21 levels and ALT (A) or AST (B) in patients with CHC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:13:57"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/718900/Figure_4.tif"], "description"=>"<p>; (B), ROC curve analysis of serum miR-21 concentration for discriminating patients with minimal (HAI<sub>A+B+C</sub>≤3) vs. moderate to severe necroinflammatory activity (HAI<sub>A+B+C</sub>>3) using dC<sub>T</sub> of miR-21; (C), relationship between serum miR-21 and fibrosis index in patients with CHC.</p>", "links"=>[], "tags"=>["serum", "mir-21", "levels", "hai"], "article_id"=>389236, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Relationship_between_serum_miR_21_levels_and_the_HAI_score_A_/389236", "title"=>"Relationship between serum miR-21 levels and the HAI score (A)", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:14:38"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/719028/Figure_5.tif"], "description"=>"<p>Validation of the relationship between the serum levels of miR-21 and ALT (A) and AST (B) in an independent cohort of 47 CHC patients.</p>", "links"=>[], "tags"=>["serum", "levels", "mir-21", "alt", "ast", "cohort", "47", "chc"], "article_id"=>389361, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Validation_of_the_relationship_between_the_serum_levels_of_miR_21_and_ALT_A_and_AST_B_in_an_independent_cohort_of_47_CHC_patients_/389361", "title"=>"Validation of the relationship between the serum levels of miR-21 and ALT (A) and AST (B) in an independent cohort of 47 CHC patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 12:15:16"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/719132/Table_3.xls"], "description"=>"<p>The HAI score used for this analysis was the sum of HAI-A, -B and -C.</p>", "links"=>[], "tags"=>["multivariate", "factors", "correlated"], "article_id"=>389472, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.t003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Uni_and_multivariate_analysis_of_factors_correlated_to_minimal_HAI_8804_3_vs_mild_to_severe_HAI_gt_3_necroinflammation_/389472", "title"=>"Uni- and multivariate analysis of factors correlated to minimal (HAI≤3) vs. mild to severe (HAI>3) necroinflammation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 12:15:51"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/719184/Table_2.xls"], "description"=>"<p>*>35 IU/l female; >50 IU/l male.</p>", "links"=>[], "tags"=>["validation", "cohort", "chc"], "article_id"=>389526, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.t002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Characteristics_of_the_independent_validation_cohort_of_CHC_patients_/389526", "title"=>"Characteristics of the independent validation cohort of CHC patients.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 12:16:07"}
  • {"files"=>["https://s3-eu-west-1.amazonaws.com/pstorage-plos-3567654/719237/Table_1.xls"], "description"=>"<p>*>35 IU/l female; >50 IU/l male.</p>", "links"=>[], "tags"=>["chc", "patients", "hcc"], "article_id"=>389582, "categories"=>["Cancer", "Chemistry"], "users"=>["Verena Bihrer", "Oliver Waidmann", "Mireen Friedrich-Rust", "Nicole Forestier", "Simone Susser", "Jörg Haupenthal", "Martin Welker", "Ying Shi", "Jan Peveling-Oberhag", "Andreas Polta", "Michael von Wagner", "Heinfried H. Radeke", "Christoph Sarrazin", "Jörg Trojan", "Stefan Zeuzem", "Bernd Kronenberger", "Albrecht Piiper"], "doi"=>["http://dx.doi.org/10.1371/journal.pone.0026971.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"http://figshare.com/articles/_Characteristics_of_CHC_patients_CHC_patients_with_HCC_and_healthy_subjects_/389582", "title"=>"Characteristics of CHC patients, CHC patients with HCC and healthy subjects.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 12:16:24"}

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