High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis
: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene , a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediatin...
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| Veröffentlicht in: | Cancers 2024-10, Vol.16 (21), p.3647 |
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| creator | Dreyer, Verena J Shi, Jia-Xin Rose, Michael Onyuro, Maureen T Steib, Florian Hilgers, Lars Seillier, Lancelot Dietrich, Jana Riese, Janik Meurer, Steffen K Weiskirchen, Ralf Neumann, Ulf Heij, Lara Luedde, Tom Loosen, Sven H Lurje, Isabella Lurje, Georg Gaisa, Nadine T Jonigk, Danny Bednarsch, Jan Dahl, Edgar Brüchle, Nadina Ortiz |
| description | : Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene
, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis.
: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA).
: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI).
: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear. |
| doi_str_mv | 10.3390/cancers16213647 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11545166</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A815344355</galeid><sourcerecordid>A815344355</sourcerecordid><originalsourceid>FETCH-LOGICAL-c332t-d341fe692297cd5289ab871395c855020f9f49d02cc8ae88ed0037338d0aded53</originalsourceid><addsrcrecordid>eNptUk1v1DAQjRCIVqVnbsgSFy7b-iOO7ROqVi27UiWQWM6W154krhJ7sZMC_x6HltJW2AePPO-9mTeaqnpL8BljCp9bEyykTBpKWFOLF9UxxYKumkbVLx_FR9Vpzje4HMaIaMTr6ogpTiSW_LhKG9_16PLnIUHOPgYUWzT1gHbzGBP6Oh_-JEr4JcUJfEDb3XbDUQnWfRxM6Hy0Jlkf4mgyWseUYDATZPTDTz0y6MrcxmT2AywCXYjZ5zfVq9YMGU7v35Pq29Xlbr1ZXX_-tF1fXK8sY3RaOVaTFhpFqRLWcSqV2UtBSutWco4pblVbK4eptdKAlOCKQcGYdNg4cJydVB_vdA_zfgRnIUzJDPqQ_GjSLx2N108zwfe6i7eaEF5z0jRF4cO9QorfZ8iTHn22MBTfEOesGaFS1IxKWaDvn0Fv4pxC8beguCoDb8Q_VGcG0D60sRS2i6i-kISzumZ8afzsP6hyHYzexgCtL_9PCOd3BJtizgnaB5ME62VV9LNVKYx3j2fzgP-7GOw32ze6pA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3125995167</pqid></control><display><type>article</type><title>High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis</title><source>PubMed Central Open Access</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><creator>Dreyer, Verena J ; Shi, Jia-Xin ; Rose, Michael ; Onyuro, Maureen T ; Steib, Florian ; Hilgers, Lars ; Seillier, Lancelot ; Dietrich, Jana ; Riese, Janik ; Meurer, Steffen K ; Weiskirchen, Ralf ; Neumann, Ulf ; Heij, Lara ; Luedde, Tom ; Loosen, Sven H ; Lurje, Isabella ; Lurje, Georg ; Gaisa, Nadine T ; Jonigk, Danny ; Bednarsch, Jan ; Dahl, Edgar ; Brüchle, Nadina Ortiz</creator><creatorcontrib>Dreyer, Verena J ; Shi, Jia-Xin ; Rose, Michael ; Onyuro, Maureen T ; Steib, Florian ; Hilgers, Lars ; Seillier, Lancelot ; Dietrich, Jana ; Riese, Janik ; Meurer, Steffen K ; Weiskirchen, Ralf ; Neumann, Ulf ; Heij, Lara ; Luedde, Tom ; Loosen, Sven H ; Lurje, Isabella ; Lurje, Georg ; Gaisa, Nadine T ; Jonigk, Danny ; Bednarsch, Jan ; Dahl, Edgar ; Brüchle, Nadina Ortiz</creatorcontrib><description>: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene
, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis.
: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA).
: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI).
: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16213647</identifier><identifier>PMID: 39518085</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Amino acids ; Antibodies ; Bile ducts ; Biopsy ; Breast cancer ; Cancer therapies ; Cholangiocarcinoma ; Datasets ; DNA methylation ; Down-regulation ; Gallbladder ; Genes ; Genomes ; Immunohistochemistry ; Laboratories ; Medical prognosis ; Pancreatic cancer ; Prognosis ; Proteins ; Trypsin ; Tumor cell lines ; Tumor suppressor genes ; Tumors</subject><ispartof>Cancers, 2024-10, Vol.16 (21), p.3647</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c332t-d341fe692297cd5289ab871395c855020f9f49d02cc8ae88ed0037338d0aded53</cites><orcidid>0009-0006-9644-5072 ; 0000-0002-4340-1117 ; 0000-0003-3888-0931 ; 0000-0002-6288-8821 ; 0009-0007-9416-1508 ; 0000-0001-8143-6452 ; 0000-0002-8923-2726 ; 0000-0003-0701-060X ; 0000-0002-4006-7707 ; 0000-0001-6704-2422 ; 0000-0002-8439-7994 ; 0000-0002-0602-3356 ; 0000-0002-2799-2287 ; 0000-0003-0821-441X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545166/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545166/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39518085$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dreyer, Verena J</creatorcontrib><creatorcontrib>Shi, Jia-Xin</creatorcontrib><creatorcontrib>Rose, Michael</creatorcontrib><creatorcontrib>Onyuro, Maureen T</creatorcontrib><creatorcontrib>Steib, Florian</creatorcontrib><creatorcontrib>Hilgers, Lars</creatorcontrib><creatorcontrib>Seillier, Lancelot</creatorcontrib><creatorcontrib>Dietrich, Jana</creatorcontrib><creatorcontrib>Riese, Janik</creatorcontrib><creatorcontrib>Meurer, Steffen K</creatorcontrib><creatorcontrib>Weiskirchen, Ralf</creatorcontrib><creatorcontrib>Neumann, Ulf</creatorcontrib><creatorcontrib>Heij, Lara</creatorcontrib><creatorcontrib>Luedde, Tom</creatorcontrib><creatorcontrib>Loosen, Sven H</creatorcontrib><creatorcontrib>Lurje, Isabella</creatorcontrib><creatorcontrib>Lurje, Georg</creatorcontrib><creatorcontrib>Gaisa, Nadine T</creatorcontrib><creatorcontrib>Jonigk, Danny</creatorcontrib><creatorcontrib>Bednarsch, Jan</creatorcontrib><creatorcontrib>Dahl, Edgar</creatorcontrib><creatorcontrib>Brüchle, Nadina Ortiz</creatorcontrib><title>High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene
, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis.
: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA).
: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI).
: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear.</description><subject>Amino acids</subject><subject>Antibodies</subject><subject>Bile ducts</subject><subject>Biopsy</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>Cholangiocarcinoma</subject><subject>Datasets</subject><subject>DNA methylation</subject><subject>Down-regulation</subject><subject>Gallbladder</subject><subject>Genes</subject><subject>Genomes</subject><subject>Immunohistochemistry</subject><subject>Laboratories</subject><subject>Medical prognosis</subject><subject>Pancreatic cancer</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Trypsin</subject><subject>Tumor cell lines</subject><subject>Tumor suppressor 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Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis</title><author>Dreyer, Verena J ; Shi, Jia-Xin ; Rose, Michael ; Onyuro, Maureen T ; Steib, Florian ; Hilgers, Lars ; Seillier, Lancelot ; Dietrich, Jana ; Riese, Janik ; Meurer, Steffen K ; Weiskirchen, Ralf ; Neumann, Ulf ; Heij, Lara ; Luedde, Tom ; Loosen, Sven H ; Lurje, Isabella ; Lurje, Georg ; Gaisa, Nadine T ; Jonigk, Danny ; Bednarsch, Jan ; Dahl, Edgar ; Brüchle, Nadina Ortiz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c332t-d341fe692297cd5289ab871395c855020f9f49d02cc8ae88ed0037338d0aded53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amino acids</topic><topic>Antibodies</topic><topic>Bile ducts</topic><topic>Biopsy</topic><topic>Breast cancer</topic><topic>Cancer therapies</topic><topic>Cholangiocarcinoma</topic><topic>Datasets</topic><topic>DNA methylation</topic><topic>Down-regulation</topic><topic>Gallbladder</topic><topic>Genes</topic><topic>Genomes</topic><topic>Immunohistochemistry</topic><topic>Laboratories</topic><topic>Medical prognosis</topic><topic>Pancreatic cancer</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>Trypsin</topic><topic>Tumor cell lines</topic><topic>Tumor suppressor genes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dreyer, Verena J</creatorcontrib><creatorcontrib>Shi, Jia-Xin</creatorcontrib><creatorcontrib>Rose, Michael</creatorcontrib><creatorcontrib>Onyuro, Maureen T</creatorcontrib><creatorcontrib>Steib, Florian</creatorcontrib><creatorcontrib>Hilgers, Lars</creatorcontrib><creatorcontrib>Seillier, Lancelot</creatorcontrib><creatorcontrib>Dietrich, Jana</creatorcontrib><creatorcontrib>Riese, Janik</creatorcontrib><creatorcontrib>Meurer, Steffen K</creatorcontrib><creatorcontrib>Weiskirchen, 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Ortiz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2024-10-29</date><risdate>2024</risdate><volume>16</volume><issue>21</issue><spage>3647</spage><pages>3647-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene
, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis.
: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA).
: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI).
: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39518085</pmid><doi>10.3390/cancers16213647</doi><orcidid>https://orcid.org/0009-0006-9644-5072</orcidid><orcidid>https://orcid.org/0000-0002-4340-1117</orcidid><orcidid>https://orcid.org/0000-0003-3888-0931</orcidid><orcidid>https://orcid.org/0000-0002-6288-8821</orcidid><orcidid>https://orcid.org/0009-0007-9416-1508</orcidid><orcidid>https://orcid.org/0000-0001-8143-6452</orcidid><orcidid>https://orcid.org/0000-0002-8923-2726</orcidid><orcidid>https://orcid.org/0000-0003-0701-060X</orcidid><orcidid>https://orcid.org/0000-0002-4006-7707</orcidid><orcidid>https://orcid.org/0000-0001-6704-2422</orcidid><orcidid>https://orcid.org/0000-0002-8439-7994</orcidid><orcidid>https://orcid.org/0000-0002-0602-3356</orcidid><orcidid>https://orcid.org/0000-0002-2799-2287</orcidid><orcidid>https://orcid.org/0000-0003-0821-441X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2024-10, Vol.16 (21), p.3647 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11545166 |
| source | PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Amino acids Antibodies Bile ducts Biopsy Breast cancer Cancer therapies Cholangiocarcinoma Datasets DNA methylation Down-regulation Gallbladder Genes Genomes Immunohistochemistry Laboratories Medical prognosis Pancreatic cancer Prognosis Proteins Trypsin Tumor cell lines Tumor suppressor genes Tumors |
| title | High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T08%3A16%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20Expression%20of%20the%20Tumor%20Suppressor%20Protein%20ITIH5%20in%20Cholangiocarcinomas%20Correlates%20with%20a%20Favorable%20Prognosis&rft.jtitle=Cancers&rft.au=Dreyer,%20Verena%20J&rft.date=2024-10-29&rft.volume=16&rft.issue=21&rft.spage=3647&rft.pages=3647-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers16213647&rft_dat=%3Cgale_pubme%3EA815344355%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3125995167&rft_id=info:pmid/39518085&rft_galeid=A815344355&rfr_iscdi=true |