RT Journal Article
T1 Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma.
A1 Oliver, Javier
A1 Onieva, Juan Luis
A1 Garrido-Barros, Maria
A1 Berciano-Guerrero, Miguel-Angel
A1 Sanchez-Muñoz, Alfonso
A1 Lozano, Maria Jose
A1 Farngren, Angela
A1 Alvarez, Martina
A1 Martinez-Galvez, Beatriz
A1 Perez-Ruiz, Elisabeth
A1 Alba, Emilio
A1 Cobo, Manuel
A1 Rueda-Dominguez, Antonio
A1 Barragan, Isabel
K1 ceRNA
K1 circRNA
K1 Cutaneous melanoma
K1 Immunotherapy
K1 lncRNA
K1 Metastasis
AB 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 programmed death cell protein 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) constituted a main breakthrough in the treatment of metastatic CM, particularly for the achievement of long-term benefits. Even though it is a very promising therapy, resistance to primary immune checkpoint blockade (ICB) arises in about 70% of CM patients treated with a CTLA-4 inhibitor, and 40-65% of CM patients administered with a PD-1-targeting treatment. Some long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are implicated in triggering pro- and anti-tumorigenic responses to various cancer treatments. The relationship between lncRNAs, circRNAs and ICB immunotherapy has not been explored in cutaneous metastatic melanoma (CMM). The aim of this pilot study is to evaluate the potential role of circRNA and lncRNA expression variability as pre-treatment predictor of the clinical response to immunotherapy in CMM patients. RNA-seq from 12 formalin-fixed paraffin-embedded (FFPE) samples from the metastatic biopsies of CMM patients treated with nivolumab was used to identify response-associated transcripts. Our findings indicate that specific lncRNAs and circRNAs, probably acting as competitive endogenous RNAs (ceRNAs), are involved in the regulatory networks of the immune response against metastatic melanoma that these patients have under treatment with nivolumab. Moreover, we established a risk score that yields predictions of the overall survival (OS) and progression-free survival (PFS) of CMM patients with high accuracy. This proof-of-principle work provides a possible insight into the function of ceRNAs, contributing to efforts to decipher the complex molecular mechanisms of ICB cancer treatment response.
PB MDPI
SN 2227-9059
YR 2022
FD 2022-09-27
LK http://hdl.handle.net/10668/20845
UL http://hdl.handle.net/10668/20845
LA en
NO Oliver J, Onieva JL, Garrido-Barros M, Berciano-Guerrero MÁ, Sánchez-Muñoz A, José Lozano M, et al. Association of Circular RNA and Long Non-Coding RNA Dysregulation with the Clinical Response to Immune Checkpoint Blockade in Cutaneous Metastatic Melanoma. Biomedicines. 2022 Sep 27;10(10):2419
NO The work is funded by Instituto de Salud Carlos III through the projects PI18/01592 and FI19-00112 (to ALI) (Co-funded by the European Regional Development Fund/European Social Fund “A way to make Europe”/”Investing in your future”), Sistema Andaluz de Salud, through the projects SA 0263/2017, Nicolás Monardes (to I.B.) and PI-0121-2020, Spanish Group of Melanoma (Award for Best Research Project 2020) (to I.B.), Fundación Bancaria Unicaja through the project C19048 (to I.B., M.C.), and Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology (to I.B., E.A.) and Consejería de Salud PI-0121-2020 (to I.B.), RH0090-2020 CSYF 2020 (to J.O.).
DS RISalud
RD Apr 18, 2025