A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients
Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.
Medienart: |
E-Artikel |
---|
Erscheinungsjahr: |
2023 |
---|---|
Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:159 |
---|---|
Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 159(2023) vom: 05. März, Seite 114272 |
Sprache: |
Englisch |
---|
Beteiligte Personen: |
Toledano-Fonseca, M [VerfasserIn] |
---|
Links: |
---|
Anmerkungen: |
Date Completed 07.02.2023 Date Revised 07.02.2023 published: Print-Electronic Citation Status MEDLINE |
---|
doi: |
10.1016/j.biopha.2023.114272 |
---|
funding: |
|
---|---|
Förderinstitution / Projekttitel: |
|
PPN (Katalog-ID): |
NLM352170905 |
---|
LEADER | 01000naa a22002652 4500 | ||
---|---|---|---|
001 | NLM352170905 | ||
003 | DE-627 | ||
005 | 20231226053114.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231226s2023 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1016/j.biopha.2023.114272 |2 doi | |
028 | 5 | 2 | |a pubmed24n1173.xml |
035 | |a (DE-627)NLM352170905 | ||
035 | |a (NLM)36706629 | ||
035 | |a (PII)S0753-3322(23)00060-4 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Toledano-Fonseca, M |e verfasserin |4 aut | |
245 | 1 | 2 | |a A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients |
264 | 1 | |c 2023 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 07.02.2023 | ||
500 | |a Date Revised 07.02.2023 | ||
500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved. | ||
520 | |a The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Aflibercept | |
650 | 4 | |a Antiangiogenic therapy | |
650 | 4 | |a Biomarkers | |
650 | 4 | |a Circulating miRNAs | |
650 | 4 | |a Colorectal cancer | |
650 | 7 | |a aflibercept |2 NLM | |
650 | 7 | |a 15C2VL427D |2 NLM | |
650 | 7 | |a Camptothecin |2 NLM | |
650 | 7 | |a XT3Z54Z28A |2 NLM | |
650 | 7 | |a Circulating MicroRNA |2 NLM | |
650 | 7 | |a Fluorouracil |2 NLM | |
650 | 7 | |a U3P01618RT |2 NLM | |
650 | 7 | |a Leucovorin |2 NLM | |
650 | 7 | |a Q573I9DVLP |2 NLM | |
650 | 7 | |a Receptors, Vascular Endothelial Growth Factor |2 NLM | |
650 | 7 | |a EC 2.7.10.1 |2 NLM | |
650 | 7 | |a Recombinant Fusion Proteins |2 NLM | |
650 | 7 | |a MicroRNAs |2 NLM | |
700 | 1 | |a Gómez-España, M A |e verfasserin |4 aut | |
700 | 1 | |a Élez, E |e verfasserin |4 aut | |
700 | 1 | |a Grávalos, C |e verfasserin |4 aut | |
700 | 1 | |a García-Alfonso, P |e verfasserin |4 aut | |
700 | 1 | |a Rodríguez, R |e verfasserin |4 aut | |
700 | 1 | |a Losa, F |e verfasserin |4 aut | |
700 | 1 | |a Alés Díaz, I |e verfasserin |4 aut | |
700 | 1 | |a Graña, B |e verfasserin |4 aut | |
700 | 1 | |a Valladares-Ayerbes, M |e verfasserin |4 aut | |
700 | 1 | |a García-Ortiz, M V |e verfasserin |4 aut | |
700 | 1 | |a Polo, E |e verfasserin |4 aut | |
700 | 1 | |a Salgado, M |e verfasserin |4 aut | |
700 | 1 | |a Rivera, F |e verfasserin |4 aut | |
700 | 1 | |a Safont, M J |e verfasserin |4 aut | |
700 | 1 | |a Salud, A |e verfasserin |4 aut | |
700 | 1 | |a Ruiz-Casado, A |e verfasserin |4 aut | |
700 | 1 | |a Tabernero, J M |e verfasserin |4 aut | |
700 | 1 | |a Riesco, M C |e verfasserin |4 aut | |
700 | 1 | |a Rodríguez-Ariza, A |e verfasserin |4 aut | |
700 | 1 | |a Aranda, E |e verfasserin |4 aut | |
700 | 0 | |a Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie |d 1984 |g 159(2023) vom: 05. März, Seite 114272 |w (DE-627)NLM012645591 |x 1950-6007 |7 nnns |
773 | 1 | 8 | |g volume:159 |g year:2023 |g day:05 |g month:03 |g pages:114272 |
856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.biopha.2023.114272 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 159 |j 2023 |b 05 |c 03 |h 114272 |