KIR and HLA Loci Are Associated with Hepatocellular Carcinoma Development in Patients with Hepatitis B Virus Infection: A Case-Control Study
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{"title"=>"KIR and HLA loci are associated with hepatocellular carcinoma development in patients with hepatitis B virus infection: A case-control study", "type"=>"journal", "authors"=>[{"first_name"=>"Ning", "last_name"=>"Pan", "scopus_author_id"=>"57193512212"}, {"first_name"=>"Wei", "last_name"=>"Jiang", "scopus_author_id"=>"36076825600"}, {"first_name"=>"Hang", "last_name"=>"Sun", "scopus_author_id"=>"57198747982"}, {"first_name"=>"Fengqin", "last_name"=>"Miao", "scopus_author_id"=>"8619485200"}, {"first_name"=>"Jie", "last_name"=>"Qiu", "scopus_author_id"=>"53983095800"}, {"first_name"=>"Hui", "last_name"=>"Jin", "scopus_author_id"=>"36664643600"}, {"first_name"=>"Jinhuan", "last_name"=>"Xu", "scopus_author_id"=>"53983324100"}, {"first_name"=>"Qian", "last_name"=>"Shi", "scopus_author_id"=>"53983448500"}, {"first_name"=>"Wei", "last_name"=>"Xie", "scopus_author_id"=>"7401940576"}, {"first_name"=>"Jianqiong", "last_name"=>"Zhang", "scopus_author_id"=>"36099765300"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"362707067", "sgr"=>"80053592374", "issn"=>"19326203", "pmid"=>"21998681", "scopus"=>"2-s2.0-80053592374", "doi"=>"10.1371/journal.pone.0025682", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"4824a72f-050b-3519-b9dc-68937a13a1cb", "abstract"=>"BACKGROUND: Natural killer (NK) cells activation has been reported to contribute to inflammation and liver injury during hepatitis B virus (HBV) infection both in transgenic mice and in patients. However, the role of NK cells in the process of HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating NK cell activation through recognition of specific human leukocyte antigen (HLA) class I allotypes.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: To investigate whether KIR and HLA genes could influence the risk of HBV-associated HCC development, 144 HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The presence of 12 loci of KIR was detected individually. HLA-A, -B, -C loci were genotyped with high-resolution. HLA-C group 1 homozygote (OR = 2.02; p = 0.005), HLA-Bw4-80I (OR = 2.67; p = 2.0E-04) and combination of full-length form and 22 bp-deleted form of KIR2DS4 (KIR2DS4/1D) (OR = 1.89; p = 0.017) were found associated with HCC incidence. When the combined effects of these three genetic factors were evaluated, more risk factors were observed correlating with higher odds ratios for HCC incidence (P trend = 7.4E-05). Because all the risk factors we found have been reported to result in high NK cell functional potential by previous studies, our observations suggest that NK cell activation may contribute to HBV-associated HCC development.\\n\\nCONCLUSIONS/SIGNIFICANCE: In conclusion, this study has identified significant associations that suggest an important role for NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC surveillance and has implications for novel personalized therapy strategy development aiming at HCC prevention in HBV-infected patients.", "link"=>"http://www.mendeley.com/research/kir-hla-loci-associated-hepatocellular-carcinoma-development-patients-hepatitis-b-virus-infection-ca", "reader_count"=>13, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>1, "Medicine and Dentistry"=>5, "Agricultural and Biological Sciences"=>6, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>6}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Germany"=>1}, "group_count"=>3}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/367779", "https://ndownloader.figshare.com/files/367843", "https://ndownloader.figshare.com/files/367900"], "description"=>"<div><h3>Background</h3><p>Natural killer (NK) cells activation has been reported to contribute to inflammation and liver injury during hepatitis B virus (HBV) infection both in transgenic mice and in patients. However, the role of NK cells in the process of HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. <em>Killer cell immunoglobulin-like receptors (KIRs</em>) are involved in regulating NK cell activation through recognition of specific <em>human leukocyte antigen</em> (<em>HLA</em>) class I allotypes.</p> <h3>Methodology/Principal Findings</h3><p>To investigate whether <em>KIR</em> and <em>HLA</em> genes could influence the risk of HBV-associated HCC development, 144 HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The presence of 12 loci of <em>KIR</em> was detected individually. <em>HLA-A</em>, <em>-B</em>, <em>-C</em> loci were genotyped with high-resolution. <em>HLA-C group 1</em> homozygote (OR = 2.02; <em>p = </em>0.005), <em>HLA-Bw4-80I</em> (OR = 2.67; <em>p = </em>2.0E-04) and combination of full-length form and 22 bp-deleted form of <em>KIR2DS4 (KIR2DS4/1D)</em> (OR = 1.89; <em>p = </em>0.017) were found associated with HCC incidence. When the combined effects of these three genetic factors were evaluated, more risk factors were observed correlating with higher odds ratios for HCC incidence (<em>P</em> trend = 7.4E-05). Because all the risk factors we found have been reported to result in high NK cell functional potential by previous studies, our observations suggest that NK cell activation may contribute to HBV-associated HCC development.</p> <h3>Conclusions/Significance</h3><p>In conclusion, this study has identified significant associations that suggest an important role for NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC surveillance and has implications for novel personalized therapy strategy development aiming at HCC prevention in HBV-infected patients.</p> </div>", "links"=>[], "tags"=>["loci", "are", "hepatocellular", "carcinoma", "patients", "hepatitis", "case-control"], "article_id"=>132658, "categories"=>["Cancer", "Chemistry", "Genetics", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0025682.s001", "https://dx.doi.org/10.1371/journal.pone.0025682.s002", "https://dx.doi.org/10.1371/journal.pone.0025682.s003"], "stats"=>{"downloads"=>1, "page_views"=>37, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_KIR_and_HLA_Loci_Are_Associated_with_Hepatocellular_Carcinoma_Development_in_Patients_with_Hepatitis_B_Virus_Infection_A_Case_Control_Study/132658", "title"=>"<em>KIR</em> and <em>HLA</em> Loci Are Associated with Hepatocellular Carcinoma Development in Patients with Hepatitis B Virus Infection: A Case-Control Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-10-05 00:44:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/727174"], "description"=>"<p>*Patient sera were tested for hepatitis A virus IgM, hepatitis C virus antibody, hepatitis D virus antigen, hepatitis D virus antibody, and hepatitis E virus IgM.</p>", "links"=>[], "tags"=>["hbv-infected", "patients", "included"], "article_id"=>397526, "categories"=>["Chemistry", "Genetics", "Infectious Diseases", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025682.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographic_and_clinical_features_of_HBV_infected_patients_included_in_the_present_study_/397526", "title"=>"Demographic and clinical features of HBV-infected patients included in the present study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-05 02:05:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/727098"], "description"=>"<p>*Of significant difference (<i>p</i><0.017) after correction.</p>†<p>determined by Fisher's exact test.</p>", "links"=>[], "tags"=>["ligands"], "article_id"=>397446, "categories"=>["Chemistry", "Genetics", "Infectious Diseases", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025682.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_HLA_C_ligands_for_KIR_with_HCC_/397446", "title"=>"Associations between <i>HLA-C</i> ligands for <i>KIR</i> with HCC.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-05 02:04:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/727020"], "description"=>"<p>ORs (circle) and 95% confidence intervals (dashes) are shown for <i>C1C1/Bw4-80/(KIR2DS4/1D)</i> separately. The referent groups, <i>C1C1-/Bw4-80-/(2DS4/1D)-</i> are those with which all other genotypically defined groups are compared, and the OR for referent group is set at 1. We listed the various genotypes separately and ordered by increasing ORs as a means to compare ORs of individual genotypes (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025682#pone.0025682.s003\" target=\"_blank\">table S3</a>). Group <i>C1C1-/Bw4-80+/(2DS4/1D)+</i> was not included because only 2 subjects in HCC group and 1 subject in control group carried this genotype.</p>", "links"=>[], "tags"=>["hcc"], "article_id"=>397367, "categories"=>["Chemistry", "Genetics", "Infectious Diseases", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025682.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Combined_effect_HLA_C1C1_Bw4_80_KIR2DS4_1D_on_HCC_occurrence_/397367", "title"=>"Combined effect <i>HLA-C1C1/Bw4-80/(KIR2DS4/1D)</i> on HCC occurrence.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:02:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/726944"], "description"=>"<p>The frequency of <i>HLA-C1C2</i> (1 copy of <i>HLA-C1</i>) was increased significantly in cirrhosis patients compared to that in HCC patients (cirrhosis vs HCC: OR = 2.95, <i>p</i> = 0.001). This increase in cirrhosis patients did not reach statistical significance level after correction when compared to that in hepatitis patients (cirrhosis vs hepatitis: OR = 2.21, <i>p</i> = 0.01). <i>HLA-C1C1</i> (2 copies of <i>HLA-C1</i>) was found more frequently in HCC patients than that in liver cirrhosis patients (HCC vs cirrhosis OR = 0.34, <i>p</i> = 0.001) (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0025682#pone.0025682.s001\" target=\"_blank\">table S1</a>). * Of significant difference (<i>p</i><0.006) after correction.</p>", "links"=>[], "tags"=>["progression", "hcc"], "article_id"=>397288, "categories"=>["Chemistry", "Genetics", "Infectious Diseases", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025682.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_copy_number_of_HLA_C1_on_disease_progression_to_HCC_development_/397288", "title"=>"Effect of copy number of <i>HLA-C1</i> on disease progression to HCC development.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-10-05 02:01:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/727211"], "description"=>"<p>*Of significant difference (<i>p</i><0.013) after correction.</p>", "links"=>[], "tags"=>["ligands"], "article_id"=>397562, "categories"=>["Chemistry", "Genetics", "Infectious Diseases", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025682.t004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_HLA_B_ligands_for_KIR_with_HCC_/397562", "title"=>"Associations between <i>HLA-B</i> ligands for <i>KIR</i> with HCC.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-05 02:06:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/727139"], "description"=>"<p>Associations between <i>KIR2DS4/1D</i> with disease progression towards HCC development.</p>", "links"=>[], "tags"=>["progression", "hcc"], "article_id"=>397486, "categories"=>["Chemistry", "Genetics", "Infectious Diseases", "Immunology"], "users"=>["Ning Pan", "Wei Jiang", "Hang Sun", "Fengqin Miao", "Jie Qiu", "Hui Jin", "Jinhuan Xu", "Qian Shi", "Wei Xie", "Jianqiong Zhang"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025682.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_KIR2DS4_1D_with_disease_progression_towards_HCC_development_/397486", "title"=>"Associations between <i>KIR2DS4/1D</i> with disease progression towards HCC development.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-10-05 02:04:46"}

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