Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer
Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expressi...
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| Veröffentlicht in: | Virchows Archiv : an international journal of pathology 2024-10, Vol.485 (4), p.655-664 |
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| container_title | Virchows Archiv : an international journal of pathology |
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| creator | Eskuri, Maarit Kemi, Niko Helminen, Olli Huhta, Heikki Kauppila, Joonas H |
| description | Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11–1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98–1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06–2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60–0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46–0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not. |
| doi_str_mv | 10.1007/s00428-023-03635-1 |
| format | Article |
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Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11–1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98–1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06–2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60–0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46–0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.</description><identifier>ISSN: 0945-6317</identifier><identifier>ISSN: 1432-2307</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s00428-023-03635-1</identifier><identifier>PMID: 37750927</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - metabolism ; Cancer ; Female ; Gastric cancer ; Histology ; Humans ; Immune system ; Immunohistochemistry ; Intestine ; Kaplan-Meier Estimate ; Male ; Medicin och hälsovetenskap ; Medicine ; Medicine & Public Health ; Middle Aged ; Multivariate analysis ; Original Article ; Pathology ; Prognosis ; Proteins ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Subgroups ; Survival ; Tissue Array Analysis ; TLR1 protein ; TLR2 protein ; TLR4 protein ; TLR5 protein ; Toll-Like Receptor 1 - analysis ; Toll-Like Receptor 1 - metabolism ; Toll-Like Receptor 2 - analysis ; Toll-Like Receptor 2 - metabolism ; Toll-Like Receptor 4 - analysis ; Toll-Like Receptor 4 - metabolism ; Toll-Like Receptor 5 - analysis ; Toll-Like Receptor 5 - metabolism ; Toll-Like Receptor 6 - analysis ; Toll-Like Receptor 6 - metabolism ; Toll-like receptors ; Toll-Like Receptors - analysis ; Toll-Like Receptors - metabolism ; Tumor cells ; Tumors</subject><ispartof>Virchows Archiv : an international journal of pathology, 2024-10, Vol.485 (4), p.655-664</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c463t-dbbfd98442bb88aac8ce14364499344a4d52ea1d78c683c1be15ac3c286a45ef3</citedby><cites>FETCH-LOGICAL-c463t-dbbfd98442bb88aac8ce14364499344a4d52ea1d78c683c1be15ac3c286a45ef3</cites><orcidid>0000-0002-6583-6891</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00428-023-03635-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00428-023-03635-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37750927$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:153733843$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Eskuri, Maarit</creatorcontrib><creatorcontrib>Kemi, Niko</creatorcontrib><creatorcontrib>Helminen, Olli</creatorcontrib><creatorcontrib>Huhta, Heikki</creatorcontrib><creatorcontrib>Kauppila, Joonas H</creatorcontrib><title>Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer</title><title>Virchows Archiv : an international journal of pathology</title><addtitle>Virchows Arch</addtitle><addtitle>Virchows Arch</addtitle><description>Toll-like receptors (TLRs) are expressed on both immune cells and tumor cells, triggering both anti-tumor and pro-tumor responses. Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11–1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98–1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06–2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60–0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46–0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Female</subject><subject>Gastric cancer</subject><subject>Histology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunohistochemistry</subject><subject>Intestine</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Original Article</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Subgroups</subject><subject>Survival</subject><subject>Tissue Array Analysis</subject><subject>TLR1 protein</subject><subject>TLR2 protein</subject><subject>TLR4 protein</subject><subject>TLR5 protein</subject><subject>Toll-Like Receptor 1 - analysis</subject><subject>Toll-Like Receptor 1 - metabolism</subject><subject>Toll-Like Receptor 2 - analysis</subject><subject>Toll-Like Receptor 2 - metabolism</subject><subject>Toll-Like Receptor 4 - analysis</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-Like Receptor 5 - analysis</subject><subject>Toll-Like Receptor 5 - metabolism</subject><subject>Toll-Like Receptor 6 - analysis</subject><subject>Toll-Like Receptor 6 - metabolism</subject><subject>Toll-like receptors</subject><subject>Toll-Like Receptors - analysis</subject><subject>Toll-Like Receptors - metabolism</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>0945-6317</issn><issn>1432-2307</issn><issn>1432-2307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1rVDEUxYModqz-Ay4k4MbFxObm5nMpxS8odNOuQ17enfLaN--NyTzE_97YmbYg6Coh-Z1zT3IYewvyI0jpzqqUWnkhFQqJFo2AZ2wFGpVQKN1ztpJBG2ER3Al7VeutlAo82JfsBJ0zMii3Yu5qHkcxDnfEC2Xa7edSOay5WnO95mbN09Rzy4eJ36S6L0PmOU2Zymv2YpPGSm-O6ym7_vL56vybuLj8-v3804XI2uJe9F236YPXWnWd9ylln6kltFqHgFon3RtFCXrns_WYoSMwKWNW3iZtaIOnTBx860_aLV3clWGbyq84pyEej-7ajqJXDpxvfPgnvytz_yR6EIJBh-g1Nu2Hg7aBPxaq-7gdaqZxTBPNS40tVFAQrHUNff8XejsvZWo_EREUuOC0N41SByqXudZCm8c4IOOfCuOhwtgqjPcVRmiid0frpdtS_yh56KwBeHxiu5puqDzN_o_tb_sYo68</recordid><startdate>20241001</startdate><enddate>20241001</enddate><creator>Eskuri, Maarit</creator><creator>Kemi, Niko</creator><creator>Helminen, Olli</creator><creator>Huhta, Heikki</creator><creator>Kauppila, Joonas H</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</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>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope><orcidid>https://orcid.org/0000-0002-6583-6891</orcidid></search><sort><creationdate>20241001</creationdate><title>Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer</title><author>Eskuri, Maarit ; 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Therefore, TLRs have potential as prognostic biomarkers and immunotherapeutic targets. The aim of this study was to investigate TLR1, TLR2, TLR4, TLR5, and TLR6 expression and association with clinicopathological variables and survival in gastric cancer. Immunohistochemical study on cancer specimens from 564 resected gastric cancer patients was performed using tissue microarrays. The association between patient survival and TLR expression was calculated with Cox regression adjusted for confounding factors. Patients with high cytoplasmic TLR2 expression had significantly poorer 5-year survival than the low cytoplasmic TLR2 expression group in multivariate analysis (adjusted HR 1.38, 95% CI 1.11–1.71), and this estimate was similar in intestinal type (adjusted HR 1.33, 95% CI 0.98–1.80) and diffuse type (adjusted HR 1.48, 95% CI 1.06–2.05) histology subgroups. Patients with high cytoplasmic TLR6 expression group had significantly better 5-year survival compared with low cytoplasmic TLR6 expression group in multivariate analysis (adjusted HR 0.74, 95% CI 0.60–0.91). In the subgroup analysis of diffuse type of histology, the 5-year survival was better in high cytoplasmic TLR6 expression group in multivariable analysis (HR 0.62, 95% CI 0.46–0.83). In the intestinal type of histology subgroup, no significant differences between the groups were present. TLR1, TLR4, and TLR5 expression were not associated with 5-year survival. In conclusion, cytoplasmic TLR2 and TLR6 expression seem to have independent prognostic impact in gastric cancer, while TLR1, TLR4, and TLR5 do not.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>37750927</pmid><doi>10.1007/s00428-023-03635-1</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-6583-6891</orcidid></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biomarkers Biomarkers, Tumor - analysis Biomarkers, Tumor - metabolism Cancer Female Gastric cancer Histology Humans Immune system Immunohistochemistry Intestine Kaplan-Meier Estimate Male Medicin och hälsovetenskap Medicine Medicine & Public Health Middle Aged Multivariate analysis Original Article Pathology Prognosis Proteins Stomach Neoplasms - metabolism Stomach Neoplasms - mortality Stomach Neoplasms - pathology Subgroups Survival Tissue Array Analysis TLR1 protein TLR2 protein TLR4 protein TLR5 protein Toll-Like Receptor 1 - analysis Toll-Like Receptor 1 - metabolism Toll-Like Receptor 2 - analysis Toll-Like Receptor 2 - metabolism Toll-Like Receptor 4 - analysis Toll-Like Receptor 4 - metabolism Toll-Like Receptor 5 - analysis Toll-Like Receptor 5 - metabolism Toll-Like Receptor 6 - analysis Toll-Like Receptor 6 - metabolism Toll-like receptors Toll-Like Receptors - analysis Toll-Like Receptors - metabolism Tumor cells Tumors |
| title | Toll-like receptors 1, 2, 4, 5, and 6 in gastric cancer |
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