Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy
Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal muc...
Gespeichert in:
| Veröffentlicht in: | Pathology, research and practice research and practice, 2020-06, Vol.216 (6), p.152945-152945, Article 152945 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 152945 |
|---|---|
| container_issue | 6 |
| container_start_page | 152945 |
| container_title | Pathology, research and practice |
| container_volume | 216 |
| creator | Stankovic, Biljana Dragasevic, Sanja Klaassen, Kristel Kotur, Nikola Srzentic Drazilov, Sanja Zukic, Branka Sokic Milutinovic, Aleksandra Milovanovic, Tamara Lukic, Snezana Popovic, Dragan Pavlovic, Sonja Nikcevic, Gordana |
| description | Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles.
From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay.
Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance.
We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients. |
| doi_str_mv | 10.1016/j.prp.2020.152945 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2389211535</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0344033819328973</els_id><sourcerecordid>2389211535</sourcerecordid><originalsourceid>FETCH-LOGICAL-c353t-e2a4dc720da3d54f7be65c3bd62892e7807963e285ae8acf2400ec1dde21d2e03</originalsourceid><addsrcrecordid>eNp9UcuOEzEQtBCIDYEP4IJ8g8sEP-YVOK2iXUBaiQuIo9WxexJHM7axPQvzMfwrDlk4cumXqqvUXYS85GzDGW_fnjYhho1govSN2NbNI7LiLe8r1kr-mKyYrOuKSdlfkWcpnRhjHav5U3Ilhei2W96vyK-bn2H00boDtW4YYZog-7hQcIZC8CH7bDVN9uAgzxFTQVFjU7ZOZ7qL_uhep_MAISENR3Q-LwHTO_oNFpr9D4gm0cmPqOcRIk05QraD1SV6R_1AQ6nQ5fRHMUM8YMZSHDFCWJ6TJwOMCV885DX5envzZfexuvv84dPu-q7SspG5QgG10Z1gBqRp6qHbY9touTet6LcCu55121ai6BvAHvQgasZQc2NQcCOQyTV5c-EN0X-fMWU12aRxHMGhn5MSsvBw3hS1NeEXqI4-pYiDCtFOEBfFmTq7ok5lEtTZFXVxpey8eqCf9xOafxt_bSiA9xcAliPvLUaVdPmKRmMj6qyMt_-h_w2d7qJZ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2389211535</pqid></control><display><type>article</type><title>Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><creator>Stankovic, Biljana ; Dragasevic, Sanja ; Klaassen, Kristel ; Kotur, Nikola ; Srzentic Drazilov, Sanja ; Zukic, Branka ; Sokic Milutinovic, Aleksandra ; Milovanovic, Tamara ; Lukic, Snezana ; Popovic, Dragan ; Pavlovic, Sonja ; Nikcevic, Gordana</creator><creatorcontrib>Stankovic, Biljana ; Dragasevic, Sanja ; Klaassen, Kristel ; Kotur, Nikola ; Srzentic Drazilov, Sanja ; Zukic, Branka ; Sokic Milutinovic, Aleksandra ; Milovanovic, Tamara ; Lukic, Snezana ; Popovic, Dragan ; Pavlovic, Sonja ; Nikcevic, Gordana</creatorcontrib><description>Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles.
From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay.
Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance.
We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.</description><identifier>ISSN: 0344-0338</identifier><identifier>EISSN: 1618-0631</identifier><identifier>DOI: 10.1016/j.prp.2020.152945</identifier><identifier>PMID: 32279918</identifier><language>eng</language><publisher>Germany: Elsevier GmbH</publisher><subject>Adult ; Apoptosis - genetics ; Crohn Disease - pathology ; Cytokines - genetics ; Female ; Humans ; Ileal Crohn's disease ; Inflammation - genetics ; Inflammation - pathology ; Intestinal Mucosa - pathology ; Male ; Middle Aged ; Molecular profiling ; Molecular Targeted Therapy ; Mucosal phenotypes ; Phenotype ; Pilot Projects ; Transcriptome ; Young Adult</subject><ispartof>Pathology, research and practice, 2020-06, Vol.216 (6), p.152945-152945, Article 152945</ispartof><rights>2020 Elsevier GmbH</rights><rights>Copyright © 2020 Elsevier GmbH. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-e2a4dc720da3d54f7be65c3bd62892e7807963e285ae8acf2400ec1dde21d2e03</citedby><cites>FETCH-LOGICAL-c353t-e2a4dc720da3d54f7be65c3bd62892e7807963e285ae8acf2400ec1dde21d2e03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0344033819328973$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32279918$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stankovic, Biljana</creatorcontrib><creatorcontrib>Dragasevic, Sanja</creatorcontrib><creatorcontrib>Klaassen, Kristel</creatorcontrib><creatorcontrib>Kotur, Nikola</creatorcontrib><creatorcontrib>Srzentic Drazilov, Sanja</creatorcontrib><creatorcontrib>Zukic, Branka</creatorcontrib><creatorcontrib>Sokic Milutinovic, Aleksandra</creatorcontrib><creatorcontrib>Milovanovic, Tamara</creatorcontrib><creatorcontrib>Lukic, Snezana</creatorcontrib><creatorcontrib>Popovic, Dragan</creatorcontrib><creatorcontrib>Pavlovic, Sonja</creatorcontrib><creatorcontrib>Nikcevic, Gordana</creatorcontrib><title>Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy</title><title>Pathology, research and practice</title><addtitle>Pathol Res Pract</addtitle><description>Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles.
From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay.
Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance.
We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.</description><subject>Adult</subject><subject>Apoptosis - genetics</subject><subject>Crohn Disease - pathology</subject><subject>Cytokines - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Ileal Crohn's disease</subject><subject>Inflammation - genetics</subject><subject>Inflammation - pathology</subject><subject>Intestinal Mucosa - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Molecular profiling</subject><subject>Molecular Targeted Therapy</subject><subject>Mucosal phenotypes</subject><subject>Phenotype</subject><subject>Pilot Projects</subject><subject>Transcriptome</subject><subject>Young Adult</subject><issn>0344-0338</issn><issn>1618-0631</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UcuOEzEQtBCIDYEP4IJ8g8sEP-YVOK2iXUBaiQuIo9WxexJHM7axPQvzMfwrDlk4cumXqqvUXYS85GzDGW_fnjYhho1govSN2NbNI7LiLe8r1kr-mKyYrOuKSdlfkWcpnRhjHav5U3Ilhei2W96vyK-bn2H00boDtW4YYZog-7hQcIZC8CH7bDVN9uAgzxFTQVFjU7ZOZ7qL_uhep_MAISENR3Q-LwHTO_oNFpr9D4gm0cmPqOcRIk05QraD1SV6R_1AQ6nQ5fRHMUM8YMZSHDFCWJ6TJwOMCV885DX5envzZfexuvv84dPu-q7SspG5QgG10Z1gBqRp6qHbY9touTet6LcCu55121ai6BvAHvQgasZQc2NQcCOQyTV5c-EN0X-fMWU12aRxHMGhn5MSsvBw3hS1NeEXqI4-pYiDCtFOEBfFmTq7ok5lEtTZFXVxpey8eqCf9xOafxt_bSiA9xcAliPvLUaVdPmKRmMj6qyMt_-h_w2d7qJZ</recordid><startdate>202006</startdate><enddate>202006</enddate><creator>Stankovic, Biljana</creator><creator>Dragasevic, Sanja</creator><creator>Klaassen, Kristel</creator><creator>Kotur, Nikola</creator><creator>Srzentic Drazilov, Sanja</creator><creator>Zukic, Branka</creator><creator>Sokic Milutinovic, Aleksandra</creator><creator>Milovanovic, Tamara</creator><creator>Lukic, Snezana</creator><creator>Popovic, Dragan</creator><creator>Pavlovic, Sonja</creator><creator>Nikcevic, Gordana</creator><general>Elsevier GmbH</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202006</creationdate><title>Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy</title><author>Stankovic, Biljana ; Dragasevic, Sanja ; Klaassen, Kristel ; Kotur, Nikola ; Srzentic Drazilov, Sanja ; Zukic, Branka ; Sokic Milutinovic, Aleksandra ; Milovanovic, Tamara ; Lukic, Snezana ; Popovic, Dragan ; Pavlovic, Sonja ; Nikcevic, Gordana</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-e2a4dc720da3d54f7be65c3bd62892e7807963e285ae8acf2400ec1dde21d2e03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Apoptosis - genetics</topic><topic>Crohn Disease - pathology</topic><topic>Cytokines - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Ileal Crohn's disease</topic><topic>Inflammation - genetics</topic><topic>Inflammation - pathology</topic><topic>Intestinal Mucosa - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Molecular profiling</topic><topic>Molecular Targeted Therapy</topic><topic>Mucosal phenotypes</topic><topic>Phenotype</topic><topic>Pilot Projects</topic><topic>Transcriptome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stankovic, Biljana</creatorcontrib><creatorcontrib>Dragasevic, Sanja</creatorcontrib><creatorcontrib>Klaassen, Kristel</creatorcontrib><creatorcontrib>Kotur, Nikola</creatorcontrib><creatorcontrib>Srzentic Drazilov, Sanja</creatorcontrib><creatorcontrib>Zukic, Branka</creatorcontrib><creatorcontrib>Sokic Milutinovic, Aleksandra</creatorcontrib><creatorcontrib>Milovanovic, Tamara</creatorcontrib><creatorcontrib>Lukic, Snezana</creatorcontrib><creatorcontrib>Popovic, Dragan</creatorcontrib><creatorcontrib>Pavlovic, Sonja</creatorcontrib><creatorcontrib>Nikcevic, Gordana</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Pathology, research and practice</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stankovic, Biljana</au><au>Dragasevic, Sanja</au><au>Klaassen, Kristel</au><au>Kotur, Nikola</au><au>Srzentic Drazilov, Sanja</au><au>Zukic, Branka</au><au>Sokic Milutinovic, Aleksandra</au><au>Milovanovic, Tamara</au><au>Lukic, Snezana</au><au>Popovic, Dragan</au><au>Pavlovic, Sonja</au><au>Nikcevic, Gordana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy</atitle><jtitle>Pathology, research and practice</jtitle><addtitle>Pathol Res Pract</addtitle><date>2020-06</date><risdate>2020</risdate><volume>216</volume><issue>6</issue><spage>152945</spage><epage>152945</epage><pages>152945-152945</pages><artnum>152945</artnum><issn>0344-0338</issn><eissn>1618-0631</eissn><abstract>Crohn's disease (CD) is chronic inflammatory bowel disease with different phenotypic characteristics influencing disease prognosis and therapeutic strategies. The aim of this pilot study was to analyze selected inflammatory and apoptotic markers in non-inflamed and inflamed samples of ileal mucosa of non-stricturing/non-penetrating (NS/NP) and stricturing (S) CD mucosal phenotypes in order to characterize their distinct profiles.
From twenty CD patients (9 NS/NP, 11 S) paired non-inflamed and inflamed ileal biopsies were collected and used for analysis of cytokine (TNF and IL6) and apoptotic (Bcl2, Bax, Fas and FasL) genes' expression levels by real-time PCR, while NFκB transcriptional potency was assessed by electromobility gel shift assay.
Our results demonstrated significant upregulation of TNF and IL6 in inflamed area of both NS/NP (p = 0.03, p = 0.01) and S phenotypes (p = 0.04, p = 0.04), respectively. However, TNF increase was more prominent in NS/NP compared to S inflamed mucosa (p = 0.02). Also, level of proapoptotic Bax was significantly higher in NS/NP compared to S inflamed mucosa (p = 0.01). Opposing transcription potency of NFκB has been detected between two phenotypes: being decreased in NS/NP (p = 0.07) and increased in S (p = 0.1) inflamed compared to non-inflamed mucosa, demonstrating trend towards statistical significance.
We found that two distinct CD phenotypes have specific molecular signatures. Obtained results could direct improvement of current and development of new therapeutic strategies based on more specific molecular stratification of CD patients.</abstract><cop>Germany</cop><pub>Elsevier GmbH</pub><pmid>32279918</pmid><doi>10.1016/j.prp.2020.152945</doi><tpages>1</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0344-0338 |
| ispartof | Pathology, research and practice, 2020-06, Vol.216 (6), p.152945-152945, Article 152945 |
| issn | 0344-0338 1618-0631 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2389211535 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Adult Apoptosis - genetics Crohn Disease - pathology Cytokines - genetics Female Humans Ileal Crohn's disease Inflammation - genetics Inflammation - pathology Intestinal Mucosa - pathology Male Middle Aged Molecular profiling Molecular Targeted Therapy Mucosal phenotypes Phenotype Pilot Projects Transcriptome Young Adult |
| title | Exploring inflammatory and apoptotic signatures in distinct Crohn's disease phenotypes: Way towards molecular stratification of patients and targeted therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T14%3A17%3A05IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Exploring%20inflammatory%20and%20apoptotic%20signatures%20in%20distinct%20Crohn's%20disease%20phenotypes:%20Way%20towards%20molecular%20stratification%20of%20patients%20and%20targeted%20therapy&rft.jtitle=Pathology,%20research%20and%20practice&rft.au=Stankovic,%20Biljana&rft.date=2020-06&rft.volume=216&rft.issue=6&rft.spage=152945&rft.epage=152945&rft.pages=152945-152945&rft.artnum=152945&rft.issn=0344-0338&rft.eissn=1618-0631&rft_id=info:doi/10.1016/j.prp.2020.152945&rft_dat=%3Cproquest_cross%3E2389211535%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2389211535&rft_id=info:pmid/32279918&rft_els_id=S0344033819328973&rfr_iscdi=true |