Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Circulating Transcriptome as a Source of Biomarkers for Melanoma

Carla Solé
,
Daniela Tramonti
,
Maike Schamm
,
Ibai Goicoechea
,
María Armesto
,
Luiza I. Hernandez
,
Lorea Manterola
,
Marta Fernandez-Mercado
,
Karmele Mujika
,
Anna Tuneu
,
Ane Jaka
,
Maitena Tellaetxe
ORCID logo ,
Marc R. Friedländer
,
Xavier Estivill
,
Paolo Piazza
,
Pablo L. Ortiz-Romero
,
Mark R. Middleton
ORCID logo ,
Charles H. lawrie
*
Version 1 : Received: 15 November 2018 / Approved: 19 November 2018 / Online: 19 November 2018 (06:49:39 CET)

A peer-reviewed article of this Preprint also exists.

Solé, C.; Tramonti, D.; Schramm, M.; Goicoechea, I.; Armesto, M.; Hernandez, L.I.; Manterola, L.; Fernandez-Mercado, M.; Mujika, K.; Tuneu, A.; Jaka, A.; Tellaetxe, M.; Friedländer, M.R.; Estivill, X.; Piazza, P.; Ortiz-Romero, P.L.; Middleton, M.R.; Lawrie, C.H. The Circulating Transcriptome as a Source of Biomarkers for Melanoma. Cancers 2019, 11, 70. Solé, C.; Tramonti, D.; Schramm, M.; Goicoechea, I.; Armesto, M.; Hernandez, L.I.; Manterola, L.; Fernandez-Mercado, M.; Mujika, K.; Tuneu, A.; Jaka, A.; Tellaetxe, M.; Friedländer, M.R.; Estivill, X.; Piazza, P.; Ortiz-Romero, P.L.; Middleton, M.R.; Lawrie, C.H. The Circulating Transcriptome as a Source of Biomarkers for Melanoma. Cancers 2019, 11, 70.

Abstract

The circulating transcriptome is a valuable source of cancer biomarkers, which with the exception of miRNAs, remains relatively unexplored. To elucidate which RNAs are present in plasma from melanoma patients and which could be used to distinguish cancer patients of 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, 5´-fragments, were enriched for the angiopoietin, 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-centre retrospective and prospective cohorts suggesting potential diagnostic use of these RNA species.

Keywords

melanoma; plasma; liquid biopsy; miRNA; mRNA; biomarker; YRNA; RNA species

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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