Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer
Abstract Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is a multifaceted, cytokine-like bioactive molecule whose levels are elevated in a wide range of inflammatory diseases and are associated with prognosis. Additionally, TIMP1 may play a role in driving systemic inflammation. TIMP1 immuno...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85549-3 |
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| author | Akseli Kehusmaa Anne Tuomisto Päivi Sirniö Henna Karjalainen Meeri Kastinen Vilja V. Tapiainen Ville K. Äijälä Taina Tervahartiala Timo Sorsa Jukka Rintala Sanna Meriläinen Juha Saarnio Tero Rautio Markus J. Mäkinen Juha P. Väyrynen |
| author_facet | Akseli Kehusmaa Anne Tuomisto Päivi Sirniö Henna Karjalainen Meeri Kastinen Vilja V. Tapiainen Ville K. Äijälä Taina Tervahartiala Timo Sorsa Jukka Rintala Sanna Meriläinen Juha Saarnio Tero Rautio Markus J. Mäkinen Juha P. Väyrynen |
| author_sort | Akseli Kehusmaa |
| collection | DOAJ |
| description | Abstract Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is a multifaceted, cytokine-like bioactive molecule whose levels are elevated in a wide range of inflammatory diseases and are associated with prognosis. Additionally, TIMP1 may play a role in driving systemic inflammation. TIMP1 immunohistochemistry and TIMP1 serum concentrations were analyzed in a cohort of 776 colorectal cancer patients. TIMP1 histoscore by cell type (tumor cell, other) was quantified using digital image analysis. Serum TIMP1 levels were evaluated for correlations with tumor TIMP1 expression, and their associations with tumor characteristics, inflammation, and prognosis were investigated. High serum TIMP1 concentrations associated with shorter overall survival (multivariable HR 1.85, 95% CI 1.30–2.65). Serum TIMP1 levels positively correlated with markers of systemic inflammation and tumor necrosis percentage but not with TIMP1 expression in tumor tissue. High TIMP1 intensity in tumor stroma associated with longer cancer-specific and overall survival in univariable analysis but not in multivariable models. T cell densities in tumor tissue positively correlated with tumor stromal TIMP1 expression and negatively with tumor epithelial TIMP1 expression. Serum TIMP1 levels show promise as a prognostic marker for colorectal cancer and correlate with systemic inflammatory markers, but do not correlate with TIMP1 expression in tumor tissue. |
| format | Article |
| id | doaj-art-a9b423ec6b6c4f2686c8fe134117da68 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-a9b423ec6b6c4f2686c8fe134117da682025-01-12T12:22:49ZengNature PortfolioScientific Reports2045-23222025-01-0115111010.1038/s41598-025-85549-3Associations of serum and tissue TIMP1 with host response and survival in colorectal cancerAkseli Kehusmaa0Anne Tuomisto1Päivi Sirniö2Henna Karjalainen3Meeri Kastinen4Vilja V. Tapiainen5Ville K. Äijälä6Taina Tervahartiala7Timo Sorsa8Jukka Rintala9Sanna Meriläinen10Juha Saarnio11Tero Rautio12Markus J. Mäkinen13Juha P. Väyrynen14Translational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluDepartment of Oral and Maxillofacial Diseases, Institute of Dentistry, Helsinki University Central HospitalDepartment of Oral and Maxillofacial Diseases, Institute of Dentistry, Helsinki University Central HospitalTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluTranslational Medicine Research Unit, Medical Research Center Oulu, Oulu University Hospital, and University of OuluAbstract Tissue inhibitor of matrix metalloproteinase 1 (TIMP1) is a multifaceted, cytokine-like bioactive molecule whose levels are elevated in a wide range of inflammatory diseases and are associated with prognosis. Additionally, TIMP1 may play a role in driving systemic inflammation. TIMP1 immunohistochemistry and TIMP1 serum concentrations were analyzed in a cohort of 776 colorectal cancer patients. TIMP1 histoscore by cell type (tumor cell, other) was quantified using digital image analysis. Serum TIMP1 levels were evaluated for correlations with tumor TIMP1 expression, and their associations with tumor characteristics, inflammation, and prognosis were investigated. High serum TIMP1 concentrations associated with shorter overall survival (multivariable HR 1.85, 95% CI 1.30–2.65). Serum TIMP1 levels positively correlated with markers of systemic inflammation and tumor necrosis percentage but not with TIMP1 expression in tumor tissue. High TIMP1 intensity in tumor stroma associated with longer cancer-specific and overall survival in univariable analysis but not in multivariable models. T cell densities in tumor tissue positively correlated with tumor stromal TIMP1 expression and negatively with tumor epithelial TIMP1 expression. Serum TIMP1 levels show promise as a prognostic marker for colorectal cancer and correlate with systemic inflammatory markers, but do not correlate with TIMP1 expression in tumor tissue.https://doi.org/10.1038/s41598-025-85549-3Colorectal cancerTIMP1PrognosisImmunohistochemistrySerum biomarker |
| spellingShingle | Akseli Kehusmaa Anne Tuomisto Päivi Sirniö Henna Karjalainen Meeri Kastinen Vilja V. Tapiainen Ville K. Äijälä Taina Tervahartiala Timo Sorsa Jukka Rintala Sanna Meriläinen Juha Saarnio Tero Rautio Markus J. Mäkinen Juha P. Väyrynen Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer Scientific Reports Colorectal cancer TIMP1 Prognosis Immunohistochemistry Serum biomarker |
| title | Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer |
| title_full | Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer |
| title_fullStr | Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer |
| title_full_unstemmed | Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer |
| title_short | Associations of serum and tissue TIMP1 with host response and survival in colorectal cancer |
| title_sort | associations of serum and tissue timp1 with host response and survival in colorectal cancer |
| topic | Colorectal cancer TIMP1 Prognosis Immunohistochemistry Serum biomarker |
| url | https://doi.org/10.1038/s41598-025-85549-3 |
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