Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies
Abstract Background Metastatic uveal melanoma (mUM) is a rare malignancy and is different from metastatic cutaneous melanoma (mCM) in tumor characteristics and efficacy to immunotherapies. Tumor-specific biomarkers are required for mUM patients to monitor early disease progression on immunotherapies...
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BMC
2025-07-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-025-03451-2 |
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| author | Devayani Machiraju Christian H Ziener Elena Clementi Francisco García-Asencio Jennifer Hüllein Jasmin Richter Bénédicte Lenoir Melanie Wiecken Daniel Hübschmann Dirk Jäger Jessica C Hassel |
| author_facet | Devayani Machiraju Christian H Ziener Elena Clementi Francisco García-Asencio Jennifer Hüllein Jasmin Richter Bénédicte Lenoir Melanie Wiecken Daniel Hübschmann Dirk Jäger Jessica C Hassel |
| author_sort | Devayani Machiraju |
| collection | DOAJ |
| description | Abstract Background Metastatic uveal melanoma (mUM) is a rare malignancy and is different from metastatic cutaneous melanoma (mCM) in tumor characteristics and efficacy to immunotherapies. Tumor-specific biomarkers are required for mUM patients to monitor early disease progression on immunotherapies. Methods We investigated clinical characteristics such as liver tumor burden and routine blood tumor markers, including lactate dehydrogenase (LDH) and transaminases in patients with mUM and with liver metastasized cutaneous melanoma (LmCM), treated with immune checkpoint inhibitors (ICIs) between May 2013-February 2024. In addition, we analyzed soluble cMET (scMET) in serum samples from these patients along with a cohort of mCM patients without liver metastases (nLmCM) using ELISA. Circulating tumor DNA (ctDNA) in the plasma was analyzed using digital droplet PCR (ddPCR) in mUM patients receiving immunotherapies. scMET, ctDNA, and LDH combination was used to simultaneously monitor disease progression in ICI and tebentafusp-receiving mUM patients. Results Sixty-nine patients with mUM and seventy-six patients with LmCM were treated with either anti-PD1 monotherapy (n = 69, 48%) or ipi + nivo combination therapy (n = 76, 52%). Irrespective of the type of melanoma and type of immunotherapy, patients with liver metastasis size greater than 8cm experienced rapid disease progression. ICI-treated mUM patients with increased LDH, aspartate aminotransferase (AST), alanine transaminase (ALT), scMET, ctDNA, and rapidly growing tumors were significantly associated with treatment resistance and shorter progression-free and overall survival (p < 0.05). scMET (AUC: 0.82) outperforms LDH (AUC: 0.77) and S100 (0.68) in predicting one-year overall survival in these patients. A validation set with LmCM and nLmCM patient samples showed that increased scMET is likely a mUM-specific feature and does not predict ICI outcomes in LmCM or nLmCM patients (p > 0.05). Moreover, monitoring ctDNA and scMET in mUM patients under ICIs or tebentafusp treatment revealed the potential for early detection of disease progression. Conclusion Soluble cMET might serve as a tumor-specific biomarker to predict clinical outcomes in mUM patients. A combinational assessment of scMET and ctDNA in mUM patients’ blood offers a highly sensitive potential approach to monitor early disease progression under immunotherapies with ICI or tebentafusp. |
| format | Article |
| id | doaj-art-63ffee3b448b4d28b92567ecb7173fd3 |
| institution | Kabale University |
| issn | 1756-9966 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
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| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj-art-63ffee3b448b4d28b92567ecb7173fd32025-08-20T03:46:15ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662025-07-0144111610.1186/s13046-025-03451-2Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapiesDevayani Machiraju0Christian H Ziener1Elena Clementi2Francisco García-Asencio3Jennifer Hüllein4Jasmin Richter5Bénédicte Lenoir6Melanie Wiecken7Daniel Hübschmann8Dirk Jäger9Jessica C Hassel10Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital HeidelbergDivision of Radiology, German Cancer Research CenterOncobit AGOncobit AGComputational Oncology Group (CO), Molecular Precision Oncology Program (MPOP), German Cancer Research Center (DKFZ); National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University HospitalHeidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital HeidelbergClinical Cooperation Unit Applied Tumor Immunity, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ)Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital HeidelbergComputational Oncology Group (CO), Molecular Precision Oncology Program (MPOP), German Cancer Research Center (DKFZ); National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and Heidelberg University HospitalClinical Cooperation Unit Applied Tumor Immunity, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ)Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital HeidelbergAbstract Background Metastatic uveal melanoma (mUM) is a rare malignancy and is different from metastatic cutaneous melanoma (mCM) in tumor characteristics and efficacy to immunotherapies. Tumor-specific biomarkers are required for mUM patients to monitor early disease progression on immunotherapies. Methods We investigated clinical characteristics such as liver tumor burden and routine blood tumor markers, including lactate dehydrogenase (LDH) and transaminases in patients with mUM and with liver metastasized cutaneous melanoma (LmCM), treated with immune checkpoint inhibitors (ICIs) between May 2013-February 2024. In addition, we analyzed soluble cMET (scMET) in serum samples from these patients along with a cohort of mCM patients without liver metastases (nLmCM) using ELISA. Circulating tumor DNA (ctDNA) in the plasma was analyzed using digital droplet PCR (ddPCR) in mUM patients receiving immunotherapies. scMET, ctDNA, and LDH combination was used to simultaneously monitor disease progression in ICI and tebentafusp-receiving mUM patients. Results Sixty-nine patients with mUM and seventy-six patients with LmCM were treated with either anti-PD1 monotherapy (n = 69, 48%) or ipi + nivo combination therapy (n = 76, 52%). Irrespective of the type of melanoma and type of immunotherapy, patients with liver metastasis size greater than 8cm experienced rapid disease progression. ICI-treated mUM patients with increased LDH, aspartate aminotransferase (AST), alanine transaminase (ALT), scMET, ctDNA, and rapidly growing tumors were significantly associated with treatment resistance and shorter progression-free and overall survival (p < 0.05). scMET (AUC: 0.82) outperforms LDH (AUC: 0.77) and S100 (0.68) in predicting one-year overall survival in these patients. A validation set with LmCM and nLmCM patient samples showed that increased scMET is likely a mUM-specific feature and does not predict ICI outcomes in LmCM or nLmCM patients (p > 0.05). Moreover, monitoring ctDNA and scMET in mUM patients under ICIs or tebentafusp treatment revealed the potential for early detection of disease progression. Conclusion Soluble cMET might serve as a tumor-specific biomarker to predict clinical outcomes in mUM patients. A combinational assessment of scMET and ctDNA in mUM patients’ blood offers a highly sensitive potential approach to monitor early disease progression under immunotherapies with ICI or tebentafusp.https://doi.org/10.1186/s13046-025-03451-2Metastatic uveal melanomaLiver metastasisBiomarkersImmune checkpoint inhibitorsTebentafuspLiquid biopsy |
| spellingShingle | Devayani Machiraju Christian H Ziener Elena Clementi Francisco García-Asencio Jennifer Hüllein Jasmin Richter Bénédicte Lenoir Melanie Wiecken Daniel Hübschmann Dirk Jäger Jessica C Hassel Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies Journal of Experimental & Clinical Cancer Research Metastatic uveal melanoma Liver metastasis Biomarkers Immune checkpoint inhibitors Tebentafusp Liquid biopsy |
| title | Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies |
| title_full | Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies |
| title_fullStr | Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies |
| title_full_unstemmed | Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies |
| title_short | Monitoring soluble cMET and ctDNA in metastatic uveal melanoma patients to track early disease progression on immunotherapies |
| title_sort | monitoring soluble cmet and ctdna in metastatic uveal melanoma patients to track early disease progression on immunotherapies |
| topic | Metastatic uveal melanoma Liver metastasis Biomarkers Immune checkpoint inhibitors Tebentafusp Liquid biopsy |
| url | https://doi.org/10.1186/s13046-025-03451-2 |
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