Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Association of Circular RNA and Long Noncoding RNA Dysregulation to Clinical Response to Immunotherapy in Cutaneous Metastatic Melanoma

Javier Oliver
,
Juan Luis Onieva
ORCID logo ,
Maria Garrido-Barros
,
Miguel Berciano-Guerrero
,
Alfonso Sánchez
,
Maria Jose Lozano
,
Angela Farngren
,
Martina Álvarez
ORCID logo ,
Beatriz Martinez-Galvez
,
Elisabeth Pérez
ORCID logo ,
Emilio Alba
,
Manuel Cobo-Dols
ORCID logo ,
Antonio Rueda-Dominguez
,
Isabel Barragán
*
Version 1 : Received: 6 July 2022 / Approved: 11 July 2022 / Online: 11 July 2022 (14:14:53 CEST)

A peer-reviewed article of this Preprint also exists.

Oliver, J.; Onieva, J.L.; Garrido-Barros, M.; Berciano-Guerrero, M.-Á.; Sánchez-Muñoz, A.; José Lozano, M.; Farngren, A.; Álvarez, M.; Martínez-Gálvez, B.; Pérez-Ruiz, E.; Alba, E.; Cobo, M.; Rueda-Domínguez, A.; Barragán, I. Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockades in Cutaneous Metastatic Melanoma. Biomedicines 2022, 10, 2419. Oliver, J.; Onieva, J.L.; Garrido-Barros, M.; Berciano-Guerrero, M.-Á.; Sánchez-Muñoz, A.; José Lozano, M.; Farngren, A.; Álvarez, M.; Martínez-Gálvez, B.; Pérez-Ruiz, E.; Alba, E.; Cobo, M.; Rueda-Domínguez, A.; Barragán, I. Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockades in Cutaneous Metastatic Melanoma. Biomedicines 2022, 10, 2419.

Abstract

Cutaneous Melanoma (CM) is the most lethal form of skin cancer if it becomes metastatic, where treatment options and survival chances decrease dramatically. Immunotherapy treatments based on the immunologic checkpoint inhibitors (PD-1 and CTLA4) constituted a main breakthrough in the treatment of metastatic CM, particularly in the long-term benefit. However, several molecular pathways are responsible for the failure of this strategy in about 50-70% of CM patients. Some Long Non-coding RNAs (lncRNAs), and circular RNAs (circRNA) are implicated in triggering pro- and antitumorigenic responses to various cancer treatments. The relationship between lncRNA, circRNA and Immune Checkpoint Blockade (ICB) immunotherapy is not extensively explored in cutaneous metastatic melanoma (CMM). The aim of this study is to evaluate the potential role of both circRNA and lncRNA as a predictive immunotherapy biomarker in CMM. RNA-seq from 12 FFPE samples from the metastatic biopsy of metastatic melanoma patients treated with Nivolumab were analyzed. Our findings indicate that specific lncRNA and circRNA are involved in regulatory networks of the immune response against metastatic melanoma under treatment with nivolumab. Moreover, we have established a risk score that allows the prediction of Overall survival (OS) and Progression-free survival (PFS) of CMM patients with high accuracy. This proof of principle work provides a possible insight on the function of ceRNA, contributing to decipher the complex molecular mechanism of ICB cancer treatment response.

Keywords

Circular RNA; Cutaneous Melanoma; Immunotherapy; metastasis; LncRNA; ecRNA

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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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