Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy

Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outco...
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Autor*in:	Lauretta Levati [verfasserIn] Cristian Bassi [verfasserIn] Simona Mastroeni [verfasserIn] Laura Lupini [verfasserIn] Gian Carlo Antonini Cappellini [verfasserIn] Laura Bonmassar [verfasserIn] Ester Alvino [verfasserIn] Simona Caporali [verfasserIn] Pedro Miguel Lacal [verfasserIn] Maria Grazia Narducci [verfasserIn] Ivan Molineris [verfasserIn] Federica De Galitiis [verfasserIn] Massimo Negrini [verfasserIn] Giandomenico Russo [verfasserIn] Stefania D’Atri [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance

Übergeordnetes Werk:	In: Cancers - MDPI AG, 2010, 14(2022), 15, p 3706
Übergeordnetes Werk:	volume:14 ; year:2022 ; number:15, p 3706

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/cancers14153706

Katalog-ID:	DOAJ01671248X

Internformat


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allfields	10.3390/cancers14153706 doi (DE-627)DOAJ01671248X (DE-599)DOAJe39091af471049918650cd5a73305b40 DE-627 ger DE-627 rakwb eng RC254-282 Lauretta Levati verfasserin aut Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management. circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cristian Bassi verfasserin aut Simona Mastroeni verfasserin aut Laura Lupini verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Laura Bonmassar verfasserin aut Ester Alvino verfasserin aut Simona Caporali verfasserin aut Pedro Miguel Lacal verfasserin aut Maria Grazia Narducci verfasserin aut Ivan Molineris verfasserin aut Federica De Galitiis verfasserin aut Massimo Negrini verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Cancers MDPI AG, 2010 14(2022), 15, p 3706 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:15, p 3706 https://doi.org/10.3390/cancers14153706 kostenfrei https://doaj.org/article/e39091af471049918650cd5a73305b40 kostenfrei https://www.mdpi.com/2072-6694/14/15/3706 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 15, p 3706
spelling	10.3390/cancers14153706 doi (DE-627)DOAJ01671248X (DE-599)DOAJe39091af471049918650cd5a73305b40 DE-627 ger DE-627 rakwb eng RC254-282 Lauretta Levati verfasserin aut Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management. circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cristian Bassi verfasserin aut Simona Mastroeni verfasserin aut Laura Lupini verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Laura Bonmassar verfasserin aut Ester Alvino verfasserin aut Simona Caporali verfasserin aut Pedro Miguel Lacal verfasserin aut Maria Grazia Narducci verfasserin aut Ivan Molineris verfasserin aut Federica De Galitiis verfasserin aut Massimo Negrini verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Cancers MDPI AG, 2010 14(2022), 15, p 3706 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:15, p 3706 https://doi.org/10.3390/cancers14153706 kostenfrei https://doaj.org/article/e39091af471049918650cd5a73305b40 kostenfrei https://www.mdpi.com/2072-6694/14/15/3706 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 15, p 3706
allfields_unstemmed	10.3390/cancers14153706 doi (DE-627)DOAJ01671248X (DE-599)DOAJe39091af471049918650cd5a73305b40 DE-627 ger DE-627 rakwb eng RC254-282 Lauretta Levati verfasserin aut Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management. circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cristian Bassi verfasserin aut Simona Mastroeni verfasserin aut Laura Lupini verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Laura Bonmassar verfasserin aut Ester Alvino verfasserin aut Simona Caporali verfasserin aut Pedro Miguel Lacal verfasserin aut Maria Grazia Narducci verfasserin aut Ivan Molineris verfasserin aut Federica De Galitiis verfasserin aut Massimo Negrini verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Cancers MDPI AG, 2010 14(2022), 15, p 3706 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:15, p 3706 https://doi.org/10.3390/cancers14153706 kostenfrei https://doaj.org/article/e39091af471049918650cd5a73305b40 kostenfrei https://www.mdpi.com/2072-6694/14/15/3706 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 15, p 3706
allfieldsGer	10.3390/cancers14153706 doi (DE-627)DOAJ01671248X (DE-599)DOAJe39091af471049918650cd5a73305b40 DE-627 ger DE-627 rakwb eng RC254-282 Lauretta Levati verfasserin aut Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management. circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cristian Bassi verfasserin aut Simona Mastroeni verfasserin aut Laura Lupini verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Laura Bonmassar verfasserin aut Ester Alvino verfasserin aut Simona Caporali verfasserin aut Pedro Miguel Lacal verfasserin aut Maria Grazia Narducci verfasserin aut Ivan Molineris verfasserin aut Federica De Galitiis verfasserin aut Massimo Negrini verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Cancers MDPI AG, 2010 14(2022), 15, p 3706 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:15, p 3706 https://doi.org/10.3390/cancers14153706 kostenfrei https://doaj.org/article/e39091af471049918650cd5a73305b40 kostenfrei https://www.mdpi.com/2072-6694/14/15/3706 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 15, p 3706
allfieldsSound	10.3390/cancers14153706 doi (DE-627)DOAJ01671248X (DE-599)DOAJe39091af471049918650cd5a73305b40 DE-627 ger DE-627 rakwb eng RC254-282 Lauretta Levati verfasserin aut Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management. circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cristian Bassi verfasserin aut Simona Mastroeni verfasserin aut Laura Lupini verfasserin aut Gian Carlo Antonini Cappellini verfasserin aut Laura Bonmassar verfasserin aut Ester Alvino verfasserin aut Simona Caporali verfasserin aut Pedro Miguel Lacal verfasserin aut Maria Grazia Narducci verfasserin aut Ivan Molineris verfasserin aut Federica De Galitiis verfasserin aut Massimo Negrini verfasserin aut Giandomenico Russo verfasserin aut Stefania D’Atri verfasserin aut In Cancers MDPI AG, 2010 14(2022), 15, p 3706 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:15, p 3706 https://doi.org/10.3390/cancers14153706 kostenfrei https://doaj.org/article/e39091af471049918650cd5a73305b40 kostenfrei https://www.mdpi.com/2072-6694/14/15/3706 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 15, p 3706
language	English
source	In Cancers 14(2022), 15, p 3706 volume:14 year:2022 number:15, p 3706
sourceStr	In Cancers 14(2022), 15, p 3706 volume:14 year:2022 number:15, p 3706
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens
isfreeaccess_bool	true
container_title	Cancers
authorswithroles_txt_mv	Lauretta Levati @@aut@@ Cristian Bassi @@aut@@ Simona Mastroeni @@aut@@ Laura Lupini @@aut@@ Gian Carlo Antonini Cappellini @@aut@@ Laura Bonmassar @@aut@@ Ester Alvino @@aut@@ Simona Caporali @@aut@@ Pedro Miguel Lacal @@aut@@ Maria Grazia Narducci @@aut@@ Ivan Molineris @@aut@@ Federica De Galitiis @@aut@@ Massimo Negrini @@aut@@ Giandomenico Russo @@aut@@ Stefania D’Atri @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	614095670
id	DOAJ01671248X
language_de	englisch
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callnumber-first	R - Medicine
author	Lauretta Levati
spellingShingle	Lauretta Levati misc RC254-282 misc circulating miRNAs misc melanoma misc BRAF inhibitors misc MEK inhibitors misc resistance misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
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topic_title	RC254-282 Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy circulating miRNAs melanoma BRAF inhibitors MEK inhibitors resistance
topic	misc RC254-282 misc circulating miRNAs misc melanoma misc BRAF inhibitors misc MEK inhibitors misc resistance misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_unstemmed	misc RC254-282 misc circulating miRNAs misc melanoma misc BRAF inhibitors misc MEK inhibitors misc resistance misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
topic_browse	misc RC254-282 misc circulating miRNAs misc melanoma misc BRAF inhibitors misc MEK inhibitors misc resistance misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens
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title	Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
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title_full	Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
author_sort	Lauretta Levati
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author_browse	Lauretta Levati Cristian Bassi Simona Mastroeni Laura Lupini Gian Carlo Antonini Cappellini Laura Bonmassar Ester Alvino Simona Caporali Pedro Miguel Lacal Maria Grazia Narducci Ivan Molineris Federica De Galitiis Massimo Negrini Giandomenico Russo Stefania D’Atri
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author-letter	Lauretta Levati
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title_sort	circulating mir-1246 and mir-485-3p as promising biomarkers of clinical response and outcome in melanoma patients treated with targeted therapy
callnumber	RC254-282
title_auth	Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
abstract	Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management.
abstractGer	Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management.
abstract_unstemmed	Despite the significant improvements in advanced melanoma therapy, there is still a pressing need for biomarkers that can predict patient response and prognosis, and therefore support rational treatment decisions. Here, we investigated whether circulating miRNAs could be biomarkers of clinical outcomes in patients treated with targeted therapy. Using next-generation sequencing, we profiled plasma miRNAs at baseline and at progression in patients treated with BRAF inhibitors (BRAFi) or BRAFi + MEKi. Selected miRNAs associated with response to therapy were subjected to validation by real-time quantitative RT-PCR. Receiver Operating Characteristics (ROC), Kaplan–Meier and univariate and multivariate Cox regression analyses were performed on the validated miR-1246 and miR-485-3p baseline levels. The median baseline levels of miR-1246 and miR-485-3p were significantly higher and lower, respectively, in the group of patients not responding to therapy (NRs) as compared with the group of responding patients (Rs). In Rs, a trend toward an increase in miR-1246 and a decrease in miR-485-3p was observed at progression. Baseline miR-1246 level and the miR-1246/miR-485-3p ratio showed a good ability to discriminate between Rs and NRs. Poorer PFS and OS were observed in patients with unfavorable levels of at least one miRNA. In multivariate analysis, a low level of miR-485-3p and a high miR-1246/miR-485-3p ratio remained independent negative prognostic factors for PFS, while a high miR-1246/miR-485-3p ratio was associated with an increased risk of mortality, although statistical significance was not reached. Evaluation of miR-1246 and miR-485-3p baseline plasma levels might help clinicians to identify melanoma patients most likely to be unresponsive to targeted therapy or at higher risk for short-term PFS and mortality, thus improving their management.
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title_short	Circulating miR-1246 and miR-485-3p as Promising Biomarkers of Clinical Response and Outcome in Melanoma Patients Treated with Targeted Therapy
url	https://doi.org/10.3390/cancers14153706 https://doaj.org/article/e39091af471049918650cd5a73305b40 https://www.mdpi.com/2072-6694/14/15/3706 https://doaj.org/toc/2072-6694
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author2	Cristian Bassi Simona Mastroeni Laura Lupini Gian Carlo Antonini Cappellini Laura Bonmassar Ester Alvino Simona Caporali Pedro Miguel Lacal Maria Grazia Narducci Ivan Molineris Federica De Galitiis Massimo Negrini Giandomenico Russo Stefania D’Atri
author2Str	Cristian Bassi Simona Mastroeni Laura Lupini Gian Carlo Antonini Cappellini Laura Bonmassar Ester Alvino Simona Caporali Pedro Miguel Lacal Maria Grazia Narducci Ivan Molineris Federica De Galitiis Massimo Negrini Giandomenico Russo Stefania D’Atri
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