The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs
Abstract Background Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC). Methods Patients with mccRCC undergoing standard first line treatment were enrolled. Blood...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03557-7 |
| _version_ | 1798038813808787456 |
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| author | Marzia Del Re Stefania Crucitta Federico Paolieri Federico Cucchiara Elena Verzoni Francesco Bloise Raffaele Ciampi Chiara Mercinelli Annalisa Capuano Liberata Sportiello Antonia Martinetti Giuseppe Procopio Luca Galli Camillo Porta Sergio Bracarda Romano Danesi |
| author_facet | Marzia Del Re Stefania Crucitta Federico Paolieri Federico Cucchiara Elena Verzoni Francesco Bloise Raffaele Ciampi Chiara Mercinelli Annalisa Capuano Liberata Sportiello Antonia Martinetti Giuseppe Procopio Luca Galli Camillo Porta Sergio Bracarda Romano Danesi |
| author_sort | Marzia Del Re |
| collection | DOAJ |
| description | Abstract Background Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC). Methods Patients with mccRCC undergoing standard first line treatment were enrolled. Blood (12 ml) was drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) was performed on cfDNA using the Oncomine Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy findings. Results A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/μl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.008, respectively). cfDNA amount was also correlated with best response (p = 0.006). Additional cfDNA cut-points divided patients into short, intermediate and long responders, with PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p < 0.001). PFS resulted to be significantly shorter in carriers of mutant TP53 compared to not carriers (p = 0.04). Patients with high cfDNA levels and mutant TP53 have the worst PFS, while patients with low cfDNA amounts and no mutations in TP53 displayed the longest PFS (p = 0.004). Conclusions The present study demonstrates that cfDNA and TP53 are potential predictive biomarkers of response in mccRCC to be further explored in larger and/or prospective studies. |
| first_indexed | 2024-04-11T21:45:29Z |
| format | Article |
| id | doaj.art-fef037278a2f4851b867577c0a56cf60 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T21:45:29Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-fef037278a2f4851b867577c0a56cf602022-12-22T04:01:26ZengBMCJournal of Translational Medicine1479-58762022-08-012011910.1186/s12967-022-03557-7The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIsMarzia Del Re0Stefania Crucitta1Federico Paolieri2Federico Cucchiara3Elena Verzoni4Francesco Bloise5Raffaele Ciampi6Chiara Mercinelli7Annalisa Capuano8Liberata Sportiello9Antonia Martinetti10Giuseppe Procopio11Luca Galli12Camillo Porta13Sergio Bracarda14Romano Danesi15Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of PisaUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of PisaUnit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of PisaUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of PisaDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei TumoriUnit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of PisaEndocrine Unit, Department of Clinical and Experimental Medicine, University of PisaUnit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of PisaDepartment of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei TumoriDepartment of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei TumoriUnit of Medical Oncology, Department of Translational Research and New Technologies in Medicine and Surgery, University of PisaDivision of Oncology, Department of Biomedical Sciences and Human Oncology, University of BariUnit of Medical and Translational Oncology, Department of Oncology, Civil Hospital of TerniUnit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of PisaAbstract Background Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC). Methods Patients with mccRCC undergoing standard first line treatment were enrolled. Blood (12 ml) was drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) was performed on cfDNA using the Oncomine Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy findings. Results A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/μl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.008, respectively). cfDNA amount was also correlated with best response (p = 0.006). Additional cfDNA cut-points divided patients into short, intermediate and long responders, with PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p < 0.001). PFS resulted to be significantly shorter in carriers of mutant TP53 compared to not carriers (p = 0.04). Patients with high cfDNA levels and mutant TP53 have the worst PFS, while patients with low cfDNA amounts and no mutations in TP53 displayed the longest PFS (p = 0.004). Conclusions The present study demonstrates that cfDNA and TP53 are potential predictive biomarkers of response in mccRCC to be further explored in larger and/or prospective studies.https://doi.org/10.1186/s12967-022-03557-7Metastatic clear cell renal cell carcinomaBiomarkersLiquid biopsyCirculating free DNATP53Immunotherapy |
| spellingShingle | Marzia Del Re Stefania Crucitta Federico Paolieri Federico Cucchiara Elena Verzoni Francesco Bloise Raffaele Ciampi Chiara Mercinelli Annalisa Capuano Liberata Sportiello Antonia Martinetti Giuseppe Procopio Luca Galli Camillo Porta Sergio Bracarda Romano Danesi The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs Journal of Translational Medicine Metastatic clear cell renal cell carcinoma Biomarkers Liquid biopsy Circulating free DNA TP53 Immunotherapy |
| title | The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs |
| title_full | The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs |
| title_fullStr | The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs |
| title_full_unstemmed | The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs |
| title_short | The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs |
| title_sort | amount of dna combined with tp53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and vegfr tkis |
| topic | Metastatic clear cell renal cell carcinoma Biomarkers Liquid biopsy Circulating free DNA TP53 Immunotherapy |
| url | https://doi.org/10.1186/s12967-022-03557-7 |
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