The circulating transcriptome as a source of biomarkers for melanoma

TY - JOUR

T1 - The circulating transcriptome as a source of biomarkers for melanoma

AU - Solé, Carla

AU - Tramonti, Daniela

AU - Schramm, Maike

AU - Goicoechea, Ibai

AU - Armesto, María

AU - Hernandez, Luiza I.

AU - Manterola, Lorea

AU - Fernandez-Mercado, Marta

AU - Mujika, Karmele

AU - Tuneu, Anna

AU - Jaka, Ane

AU - Tellaetxe, Maitena

AU - Friedländer, Marc R.

AU - Estivill, Xavier P.

AU - Piazza, Paolo

AU - Ortiz-Romero, Pablo L.

AU - Middleton, Mark R.

AU - Lawrie, Charles H.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - The circulating transcriptome is a valuable source of cancer biomarkers, which, with the exception of microRNAs (miRNAs), remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients from healthy individuals, we used next generation sequencing (NGS), and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (p < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (p < 0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA 50-fragments were enriched for the angiopoietin, p21-activated kinase (PAK), and EIF2 pathways. Levels of ATM1, AMFR, SOS1, and CD109 gene fragments were up-regulated (p < 0.001) in melanoma samples (n = 144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1, and RNY4P25 were significantly higher in patients with stage 0 disease than either healthy controls or more advanced stage disease (p < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which, most importantly, we validated in multi-center retrospective and prospective cohorts, suggesting potential diagnostic use of these RNA species.

AB - The circulating transcriptome is a valuable source of cancer biomarkers, which, with the exception of microRNAs (miRNAs), remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients from healthy individuals, we used next generation sequencing (NGS), and validation was carried out by qPCR and/or ddPCR. We identified 442 different microRNAs in samples, eleven of which were differentially expressed (p < 0.05). Levels of miR-134-5p and miR-320a-3p were significantly down-regulated (p < 0.001) in melanoma samples (n = 96) compared to healthy controls (n = 28). Differentially expressed protein-encoding mRNA 50-fragments were enriched for the angiopoietin, p21-activated kinase (PAK), and EIF2 pathways. Levels of ATM1, AMFR, SOS1, and CD109 gene fragments were up-regulated (p < 0.001) in melanoma samples (n = 144) compared to healthy controls (n = 41) (AUC = 0.825). Over 40% of mapped reads were YRNAs, a class of non-coding RNAs that to date has been little explored. Expression levels of RNY3P1, RNY4P1, and RNY4P25 were significantly higher in patients with stage 0 disease than either healthy controls or more advanced stage disease (p < 0.001). In conclusion, we have identified a number of novel RNA biomarkers, which, most importantly, we validated in multi-center retrospective and prospective cohorts, suggesting potential diagnostic use of these RNA species.

KW - Biomarker

KW - Liquid biopsy

KW - Melanoma

KW - miRNA

KW - mRNA

KW - Plasma

KW - RNA species

KW - YRNA

UR - http://www.scopus.com/inward/record.url?scp=85060336302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060336302&partnerID=8YFLogxK

U2 - 10.3390/cancers11010070

DO - 10.3390/cancers11010070

M3 - Article

AN - SCOPUS:85060336302

VL - 11

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 1

M1 - 70

ER -