Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma
Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial–mesenchymal transition (EMT) caused by many different inducers...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-03-01
|
| Series: | The Journal of Pathology: Clinical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2056-4538.12365 |
| _version_ | 1797243031713218560 |
|---|---|
| author | Martyna Parol‐Kulczyk Justyna Durślewicz Laura Blonkowska Radosław Wujec Arkadiusz Gzil Daria Piątkowska Joanna Ligmanowska Dariusz Grzanka |
| author_facet | Martyna Parol‐Kulczyk Justyna Durślewicz Laura Blonkowska Radosław Wujec Arkadiusz Gzil Daria Piątkowska Joanna Ligmanowska Dariusz Grzanka |
| author_sort | Martyna Parol‐Kulczyk |
| collection | DOAJ |
| description | Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial–mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT‐related genes and transcription factors are associated with poor prognosis in ccRCC. EMT‐related factors suppress E‐cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), β‐catenin, and E‐cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan–Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm‐c levels compared to those with low MIFn and MIFm‐c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced‐stage ccRCC. |
| first_indexed | 2024-04-24T18:48:39Z |
| format | Article |
| id | doaj.art-91a4240292d345369ff8aa5aafaf9eaf |
| institution | Directory Open Access Journal |
| issn | 2056-4538 |
| language | English |
| last_indexed | 2024-04-24T18:48:39Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Journal of Pathology: Clinical Research |
| spelling | doaj.art-91a4240292d345369ff8aa5aafaf9eaf2024-03-27T04:38:38ZengWileyThe Journal of Pathology: Clinical Research2056-45382024-03-01102n/an/a10.1002/2056-4538.12365Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinomaMartyna Parol‐Kulczyk0Justyna Durślewicz1Laura Blonkowska2Radosław Wujec3Arkadiusz Gzil4Daria Piątkowska5Joanna Ligmanowska6Dariusz Grzanka7Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Pathophysiology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandDepartment of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz Nicolaus Copernicus University Torun PolandAbstract Clear cell renal cell carcinoma (ccRCC) is one of the most common subtypes of renal cancer, with 30% of patients presenting with systemic disease at diagnosis. This aggressiveness is a consequence of the activation of epithelial–mesenchymal transition (EMT) caused by many different inducers or regulators, signaling cascades, epigenetic regulation, and the tumor environment. Alterations in EMT‐related genes and transcription factors are associated with poor prognosis in ccRCC. EMT‐related factors suppress E‐cadherin expression and are associated with tumor progression, local invasion, and metastasis. The aim of this study was to investigate the expression levels and prognostic significance of macrophage migration inhibitory factor (MIF), β‐catenin, and E‐cadherin in ccRCC patients. We examined these proteins immunohistochemically in tumor areas and adjacent normal tissues resected from patients with ccRCC. Analysis of the cancer genome atlas (TCGA) cohort was performed to verify our results. Kaplan–Meier analysis showed that median overall survival (OS) was significantly shorter in patients with tumors exhibiting high MIFn and MIFm‐c levels compared to those with low MIFn and MIFm‐c levels (p = 0.03 and p = 0.007, respectively). In the TCGA cohort, there was a significant correlation between MIF expression and OS (p < 0.0001). In conclusion, this study provides further evidence for the biological and prognostic value of MIF in the context of EMT as a potential early prognostic marker for advanced‐stage ccRCC.https://doi.org/10.1002/2056-4538.12365EMTepithelial–mesenchymal transitionMIFmacrophage migration inhibitory factorccRCCclear cell renal cell carcinoma |
| spellingShingle | Martyna Parol‐Kulczyk Justyna Durślewicz Laura Blonkowska Radosław Wujec Arkadiusz Gzil Daria Piątkowska Joanna Ligmanowska Dariusz Grzanka Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma The Journal of Pathology: Clinical Research EMT epithelial–mesenchymal transition MIF macrophage migration inhibitory factor ccRCC clear cell renal cell carcinoma |
| title | Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma |
| title_full | Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma |
| title_fullStr | Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma |
| title_full_unstemmed | Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma |
| title_short | Macrophage migration inhibitory factor (MIF) predicts survival in patients with clear cell renal cell carcinoma |
| title_sort | macrophage migration inhibitory factor mif predicts survival in patients with clear cell renal cell carcinoma |
| topic | EMT epithelial–mesenchymal transition MIF macrophage migration inhibitory factor ccRCC clear cell renal cell carcinoma |
| url | https://doi.org/10.1002/2056-4538.12365 |
| work_keys_str_mv | AT martynaparolkulczyk macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT justynadurslewicz macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT laurablonkowska macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT radosławwujec macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT arkadiuszgzil macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT dariapiatkowska macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT joannaligmanowska macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma AT dariuszgrzanka macrophagemigrationinhibitoryfactormifpredictssurvivalinpatientswithclearcellrenalcellcarcinoma |