Stat3 Downstream Gene Product Chitinase 3-Like 1 Is a Potential Biomarker of Inflammation-induced Lung Cancer in Multiple Mouse Lung Tumor Models and Humans
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{"title"=>"Stat3 Downstream Gene Product Chitinase 3-Like 1 Is a Potential Biomarker of Inflammation-induced Lung Cancer in Multiple Mouse Lung Tumor Models and Humans", "type"=>"journal", "authors"=>[{"first_name"=>"Cong", "last_name"=>"Yan", "scopus_author_id"=>"7401746268"}, {"first_name"=>"Xinchun", "last_name"=>"Ding", "scopus_author_id"=>"55038590300"}, {"first_name"=>"Lingyan", "last_name"=>"Wu", "scopus_author_id"=>"55656822600"}, {"first_name"=>"Menggang", "last_name"=>"Yu", "scopus_author_id"=>"55585755400"}, {"first_name"=>"Peng", "last_name"=>"Qu", "scopus_author_id"=>"35730400400"}, {"first_name"=>"Hong", "last_name"=>"Du", "scopus_author_id"=>"23667111200"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"368766889", "issn"=>"19326203", "pmid"=>"23613996", "sgr"=>"84876450125", "scopus"=>"2-s2.0-84876450125", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0061984"}, "id"=>"f1d83a75-2b40-3519-9e57-05b97d914f99", "abstract"=>"Over-activation of the signal transducers and activators of the transcription 3 (Stat3) pathway in lung alveolar type II (AT II) epithelial cells induces chronic inflammation and adenocarcinoma in the lung of CCSP-rtTA/(tetO)7-CMV-Stat3C bitransgenic mice. One of Stat3 downstream genes products, chitinase 3-like 1 (CHI3L1) protein, showed increased concentration in both bronchioalveolar lavage fluid (BALF) and blood of doxycycline-treated CCSP-rtTA/(tetO)7-CMV-Stat3C bitransgenic mice. When tested in other inflammation-induced lung cancer mouse models, the CHI3L1 protein concentration was also highly increased in BALF and blood of these models with tumors. Immunohistochemical staining showed strong staining of CHI3L1 protein around tumor areas in these mouse models. Analysis of normal objects and lung cancer patients revealed a significant elevation of CHI3L1 protein concentration in human serum samples from all categories of lung cancers. Furthermore, recombinant CHI3L protein stimulated proliferation and growth of Lewis lung cancer cells. Therefore, secretory CHI3L1 plays an important role in inflammation-induced lung cancer formation and potentially serve as a biomarker for lung cancer prediction. Based on our previous publication and this work, this is the first animal study linking overexpression of CHI3L1 to various lung tumor mouse models. These models will facilitate identification of additional biomarkers to predict and verify lung cancer under various pathogenic conditions, which normally cannot be done in humans.", "link"=>"http://www.mendeley.com/research/stat3-downstream-gene-product-chitinase-3like-1-potential-biomarker-inflammationinduced-lung-cancer", "reader_count"=>12, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>5, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1031394"], "description"=>"<p>Left: CHI3L1 protein concentrations in BALF and serum of doxycycline-treated and untreated bitransgenic mice. Right: ROC (Receiver Operating Characteristic) curve analyses to determine the area under the curve (AUC). Dox-: doxycycline-untreated mice; Dox+: doxycycline-treated mice without showing lung tumor; Cancer, doxycycline-treated mice with lung tumor. <b>A)</b> c-fms-rtTA/(TetO)<sub>7</sub>-CMV-MMP12 mice. Mean ± SD in BALF (n>7), DOX -: 17.7±13.8, DOX +: 42.1±67.9, Cancer: 70.9±36.5. Mean ± SD in serum (n>7), DOX -: 39.1±25.6, DOX +: 57.7±55.5, Cancer: 232.3±110.6. The gray lines represent the mean values; <b>B)</b> c-fms-rtTA/(TetO)<sub>7</sub>-CMV-Api6 mice. Mean ± SD in BALF (n>6), DOX -: 69.6±16.6, DOX +: 73.2±28.1, Cancer: 189.9±47.2. Mean ± SD in serum (n>6), DOX -: 25.2±7.3, DOX +: 21.0±11.7, Cancer: 69.5±19.1. The gray lines represent the mean values.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "chi3l1", "balf", "serum", "systemic", "inflammation-induced"], "article_id"=>687872, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g004", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISA_analyses_of_CHI3L1_protein_in_BALF_and_serum_of_systemic_inflammation_induced_lung_tumor_mice_/687872", "title"=>"ELISA analyses of CHI3L1 protein in BALF and serum of systemic inflammation-induced lung tumor mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031396"], "description"=>"<p><b>A)</b> Immunohistochemical staining in the lungs of doxycycline-treated or untreated CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Stat3C mice; <b>B)</b> Immunohistochemical staining of tumor regions in the lungs of doxycycline-treated CCSP-rtTA/(TetO)<sub>7</sub>-CMV-MMP12 mice, c-fms-rtTA/(TetO)<sub>7</sub>-CMV-MMP12 mice, and c-fms-rtTA/(TetO)<sub>7</sub>-CMV-Api6 mice. -Dox: doxycycline-untreated mice; +Dox: doxycycline-treated mice.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "staining", "chi3l1", "inflammation-induced"], "article_id"=>687873, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g005", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunohistochemical_staining_of_CHI3L1_protein_in_the_lung_of_inflammation_induced_tumor_mice_/687873", "title"=>"Immunohistochemical staining of CHI3L1 protein in the lung of inflammation-induced tumor mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031397"], "description"=>"<p>CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Stat3C bitransgenic mice were treated (+DOX) or untreated (-DOX) with doxycycline. Immunofluorescent staining of lung sections was performed using anti-CHI3L1 and F4/80 antibodies. Co-localization of both staining was observed in the merged picture. Bar represents 20 µm.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "co-staining", "chi3l1"], "article_id"=>687874, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Immunofluorescent_co_staining_of_CHI3L1_and_F4_80_in_the_lung_of_CCSP_rtTA_TetO_7_CMV_Stat3C_mice_/687874", "title"=>"Immunofluorescent co-staining of CHI3L1 and F4/80 in the lung of CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Stat3C mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031399"], "description"=>"<p><b>A)</b> Purity of recombinant CHI3L1-Flag fusion protein (upper arrow); <b>B)</b> LLC cell proliferation treated with GST or CHI3L1-GST fusion protein; <b>C)</b> The apoptotic activity of LLC cells treated with GST or CHI3L1-GST fusion protein by Annexin V labeling assay. *, p<0.05, **, P<0.01.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "chi3l1", "cells"], "article_id"=>687875, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g007", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stimulatory_effect_of_CHI3L1_on_tumor_cells_in_vitro_/687875", "title"=>"Stimulatory effect of CHI3L1 on tumor cells <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031400"], "description"=>"<p>Top: CHI3L1 protein concentrations in human serum. Bottom: ROC (Receiver Operating Characteristic) curve analysis to determine the area under the curve (AUC). Mean ± SD in control (n>30): 17.3±7.8. Mean ± SD in adenocarcinoma (n>30): 66.9±64.8. Mean ± SD in squamous carcinoma (n>30): 69.3±69.0. Mean ± SD in small cell cancer (n>30): 56.3±58.8. The gray lines represent the mean values. Control: Normal human without cancer.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "chi3l1", "serum", "cancer"], "article_id"=>687876, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g008", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISA_analysis_of_CHI3L1_protein_in_serum_of_human_lung_cancer_patients_/687876", "title"=>"ELISA analysis of CHI3L1 protein in serum of human lung cancer patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031390"], "description"=>"<p><b>A)</b> Expression of Stat3C-Flag in the whole lung of CCSP-rtTA/(tetO)7-CMV-Stat3C double-transgenic mice. Actin was used as control. WT: wild type mouse lungs; -Dox: doxycycline untreated bouble transgenic mouse lungs; +Dox1 & +Dox2: doxycycline treated mouse lungs. <b>B)</b> Expression of CHI3L1 protein in BALF of CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Stat3C double-transgenic mice. Lane 1–3, doxycycline-untreated mice (Dox-); Lane 4–6, doxycycline-treated mice without showing lung tumor (Dox+); Lane 7–10, doxycycline-treated mice showing lung tumor (Lung Cancer).</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "blot", "stat3c-flag", "chi3l1"], "article_id"=>687869, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g001", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Western_Blot_analysis_of_Stat3C_Flag_and_CHI3L1_protein_in_CCSP_rtTA_TetO_7_CMV_Stat3C_mice_/687869", "title"=>"Western Blot analysis of Stat3C-Flag and CHI3L1 protein in CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Stat3C mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031392"], "description"=>"<p>Left: CHI3L1 protein concentrations in BALF and serum of doxycycline-treated and untreated bitransgenic mice. Right: ROC (Receiver Operating Characteristic) curve analyses to determine the area under the curve (AUC). Dox-: doxycycline-untreated mice; Dox+: doxycycline-treated mice without showing lung tumor; Cancer, doxycycline-treated mice with lung tumor. Mean ± SD in BALF (n>13), DOX -: 8.8±10.0, DOX +: 100.0±49.0, Cancer: 151.8±67.3. Mean ± SD in serum (n>13), DOX -: 6.2±3.7, DOX +: 33.5±35.6, Cancer: 159.0±90.0. The gray lines represent the mean values.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "chi3l1", "balf", "serum", "bitransgenic"], "article_id"=>687870, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g002", "stats"=>{"downloads"=>8, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISA_analyses_of_CHI3L1_protein_in_BALF_and_serum_of_CCSP_rtTA_TetO_7_CMV_Stat3C_bitransgenic_mice_/687870", "title"=>"ELISA analyses of CHI3L1 protein in BALF and serum of CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Stat3C bitransgenic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/1031393"], "description"=>"<p>Left: CHI3L1 protein concentrations in BALF and serum of doxycycline-treated and untreated bitransgenic mice. Right: ROC (Receiver Operating Characteristic) curve analyses to determine the area under the curve (AUC). Dox-: doxycycline-untreated mice; Dox+: doxycycline-treated mice without showing lung tumor; Cancer, doxycycline-treated mice with lung tumor. <b>A)</b> CCSP-rtTA/(TetO)<sub>7</sub>-CMV-MMP12 mice. Mean ± SD in BALF (n>7), DOX -: 49.6±22.8, DOX +: 49.4±18.1, Cancer: 159.7±22.4. Mean ± SD in serum (n>7), DOX -: 18.6±10.9, DOX +: 18.2±4.6, Cancer: 61.4±33.5. The gray lines represent the mean values; <b>B)</b> CCSP-rtTA/(TetO)<sub>7</sub>-CMV-Api6 mice. Mean ± SD in BALF (n>3), DOX -: 82.4±37.1, DOX +: 93.8±23.0, Cancer: 409.8±49.2. Mean ± SD in serum (n>3), DOX -: 14.0±7.2, DOX +: 30.7±43.1, Cancer: 295.2±194.0. The gray lines represent the mean values.</p>", "links"=>[], "tags"=>["Biochemistry", "histology", "immunology", "oncology", "Cancer detection and diagnosis", "Early detection", "chi3l1", "balf", "serum", "inflammation-induced"], "article_id"=>687871, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Cong Yan", "Xinchun Ding", "Lingyan Wu", "Menggang Yu", "Peng Qu", "Hong Du"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0061984.g003", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_ELISA_analyses_of_CHI3L1_protein_in_BALF_and_serum_of_regional_inflammation_induced_lung_tumor_mice_/687871", "title"=>"ELISA analyses of CHI3L1 protein in BALF and serum of regional inflammation-induced lung tumor mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-04-22 02:11:11"}

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Relative Metric

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