Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer
BackgroundProstate cancer (PCa) is a highly heterogeneous disease, ranging from indolent to highly aggressive forms. Ongoing research focuses on identifying new biomarkers to improve early risk stratification in PCa, addressing current limitations to accurately evaluate disease progression. A promis...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1572299/full |
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| author | Samaneh Eickelschulte Samaneh Eickelschulte Samaneh Eickelschulte Adam Kaczorowski Florian Janke Anja Lisa Riediger Anja Lisa Riediger Anja Lisa Riediger Anja Lisa Riediger Olga Lazareva Olga Lazareva Sarah Böning Glen Kristiansen Constantin Schwab Constantin Schwab Albrecht Stenzinger Holger Sültmann Holger Sültmann Stefan Duensing Anette Duensing Magdalena Görtz Magdalena Görtz |
| author_facet | Samaneh Eickelschulte Samaneh Eickelschulte Samaneh Eickelschulte Adam Kaczorowski Florian Janke Anja Lisa Riediger Anja Lisa Riediger Anja Lisa Riediger Anja Lisa Riediger Olga Lazareva Olga Lazareva Sarah Böning Glen Kristiansen Constantin Schwab Constantin Schwab Albrecht Stenzinger Holger Sültmann Holger Sültmann Stefan Duensing Anette Duensing Magdalena Görtz Magdalena Görtz |
| author_sort | Samaneh Eickelschulte |
| collection | DOAJ |
| description | BackgroundProstate cancer (PCa) is a highly heterogeneous disease, ranging from indolent to highly aggressive forms. Ongoing research focuses on identifying new biomarkers to improve early risk stratification in PCa, addressing current limitations to accurately evaluate disease progression. A promising new approach to aid PCa risk stratification is digital spatial profiling (DSP) of PCa tissue.MethodsA total of 94 regions of interest from 38 PCa patients at first diagnosis were analyzed for the expression of 44 proteins, including components of the PI3K/AKT, MAPK, and cell death signaling pathways as well as immune cell markers. An additional validation cohort consisting of 154 PCa patients with long-term follow-up data was analyzed using immunohistochemistry (IHC) to assess the consistency of the identified biomarkers across a larger sample set.ResultsDSP identified the proliferation marker Ki-67 and phosphorylated c-Jun N-terminal protein kinase T183/Y185 (p-JNK), a member of the MAPK signaling pathway, as significantly upregulated proteins in aggressive PCa (Gleason grades 4 or 5) compared to indolent disease (Gleason grade 3; p<0.05). The upregulation of p-JNK was confirmed by IHC. High p-JNK expression was associated with a shorter time to biochemical recurrence (log-rank, p=0.1).ConclusionOur results indicate that p-JNK may contribute to PCa progression and serve as an early biomarker for aggressive PCa stratification. Identification of this biomarker through DSP could prove crucial in advancing disease management and addressing the critical unmet need for more targeted therapies in the treatment of PCa. Further studies are warranted to evaluate the role of p-JNK in PCa progression. |
| format | Article |
| id | doaj-art-e01da481280040218ccd87b0dd923d4f |
| institution | DOAJ |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-e01da481280040218ccd87b0dd923d4f2025-08-20T03:07:54ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15722991572299Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancerSamaneh Eickelschulte0Samaneh Eickelschulte1Samaneh Eickelschulte2Adam Kaczorowski3Florian Janke4Anja Lisa Riediger5Anja Lisa Riediger6Anja Lisa Riediger7Anja Lisa Riediger8Olga Lazareva9Olga Lazareva10Sarah Böning11Glen Kristiansen12Constantin Schwab13Constantin Schwab14Albrecht Stenzinger15Holger Sültmann16Holger Sültmann17Stefan Duensing18Anette Duensing19Magdalena Görtz20Magdalena Görtz21Junior Clinical Cooperation Unit, Multiparametric Methods for Early Detection of Prostate Cancer, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Urology, Heidelberg University Hospital, Heidelberg, GermanyDivision of Cancer Genome Research, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, GermanyMolecular Urooncology, Department of Urology, Heidelberg University Hospital, Heidelberg, GermanyDivision of Cancer Genome Research, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, GermanyJunior Clinical Cooperation Unit, Multiparametric Methods for Early Detection of Prostate Cancer, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Urology, Heidelberg University Hospital, Heidelberg, GermanyDivision of Cancer Genome Research, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, GermanyFaculty of Biosciences, Heidelberg University, Heidelberg, GermanyJunior Clinical Cooperation Unit, Multiparametric Methods for Early Detection of Prostate Cancer, German Cancer Research Center (DKFZ), Heidelberg, GermanyDivision of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, GermanyMolecular Urooncology, Department of Urology, Heidelberg University Hospital, Heidelberg, GermanyInstitute of Pathology, University Hospital Bonn, Bonn, GermanyInstitute of Pathology, Heidelberg University, Heidelberg, GermanyInstitute of Pathology, Tissue Bank of the National Center for Tumor Diseases (NCT), Heidelberg, GermanyInstitute of Pathology, Heidelberg University, Heidelberg, GermanyDivision of Cancer Genome Research, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany0German Cancer Consortium (DKTK), Heidelberg, GermanyMolecular Urooncology, Department of Urology, Heidelberg University Hospital, Heidelberg, Germany1Precision Oncology of Urological Malignancies, Department of Urology, Heidelberg University Hospital, Heidelberg, GermanyJunior Clinical Cooperation Unit, Multiparametric Methods for Early Detection of Prostate Cancer, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Urology, Heidelberg University Hospital, Heidelberg, GermanyBackgroundProstate cancer (PCa) is a highly heterogeneous disease, ranging from indolent to highly aggressive forms. Ongoing research focuses on identifying new biomarkers to improve early risk stratification in PCa, addressing current limitations to accurately evaluate disease progression. A promising new approach to aid PCa risk stratification is digital spatial profiling (DSP) of PCa tissue.MethodsA total of 94 regions of interest from 38 PCa patients at first diagnosis were analyzed for the expression of 44 proteins, including components of the PI3K/AKT, MAPK, and cell death signaling pathways as well as immune cell markers. An additional validation cohort consisting of 154 PCa patients with long-term follow-up data was analyzed using immunohistochemistry (IHC) to assess the consistency of the identified biomarkers across a larger sample set.ResultsDSP identified the proliferation marker Ki-67 and phosphorylated c-Jun N-terminal protein kinase T183/Y185 (p-JNK), a member of the MAPK signaling pathway, as significantly upregulated proteins in aggressive PCa (Gleason grades 4 or 5) compared to indolent disease (Gleason grade 3; p<0.05). The upregulation of p-JNK was confirmed by IHC. High p-JNK expression was associated with a shorter time to biochemical recurrence (log-rank, p=0.1).ConclusionOur results indicate that p-JNK may contribute to PCa progression and serve as an early biomarker for aggressive PCa stratification. Identification of this biomarker through DSP could prove crucial in advancing disease management and addressing the critical unmet need for more targeted therapies in the treatment of PCa. Further studies are warranted to evaluate the role of p-JNK in PCa progression.https://www.frontiersin.org/articles/10.3389/fonc.2025.1572299/fullprostate cancerdigital spatial profiling (DSP)p-JNKrisk stratificationbiomarker discovery |
| spellingShingle | Samaneh Eickelschulte Samaneh Eickelschulte Samaneh Eickelschulte Adam Kaczorowski Florian Janke Anja Lisa Riediger Anja Lisa Riediger Anja Lisa Riediger Anja Lisa Riediger Olga Lazareva Olga Lazareva Sarah Böning Glen Kristiansen Constantin Schwab Constantin Schwab Albrecht Stenzinger Holger Sültmann Holger Sültmann Stefan Duensing Anette Duensing Magdalena Görtz Magdalena Görtz Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer Frontiers in Oncology prostate cancer digital spatial profiling (DSP) p-JNK risk stratification biomarker discovery |
| title | Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer |
| title_full | Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer |
| title_fullStr | Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer |
| title_full_unstemmed | Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer |
| title_short | Digital spatial profiling identifies phospho-JNK as a biomarker for early risk stratification of aggressive prostate cancer |
| title_sort | digital spatial profiling identifies phospho jnk as a biomarker for early risk stratification of aggressive prostate cancer |
| topic | prostate cancer digital spatial profiling (DSP) p-JNK risk stratification biomarker discovery |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1572299/full |
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