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A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma

Purpose: Polymorphisms of genes in the platelet-derived growth factor (PDGF) signaling pathway have been found to predict cutaneous melanoma (CM) survival, but their clinical effects in acral melanoma (AM) patients have not been explored. The aim of this study was to characterize the functional effe...

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Autores principales: Dai, Jie, Yang, Lu, Xu, Tianxiao, Si, Lu, Cui, Chuanliang, Sheng, Xinan, Chi, Zhihong, Mao, Lili, Lian, Bin, Tang, Bixia, Bai, Xue, Zhou, Li, Li, Siming, Wang, Xuan, Yan, Xieqiao, Kong, Yan, Guo, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086247/
https://www.ncbi.nlm.nih.gov/pubmed/32226509
http://dx.doi.org/10.7150/jca.43010
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author Dai, Jie
Yang, Lu
Xu, Tianxiao
Si, Lu
Cui, Chuanliang
Sheng, Xinan
Chi, Zhihong
Mao, Lili
Lian, Bin
Tang, Bixia
Bai, Xue
Zhou, Li
Li, Siming
Wang, Xuan
Yan, Xieqiao
Kong, Yan
Guo, Jun
author_facet Dai, Jie
Yang, Lu
Xu, Tianxiao
Si, Lu
Cui, Chuanliang
Sheng, Xinan
Chi, Zhihong
Mao, Lili
Lian, Bin
Tang, Bixia
Bai, Xue
Zhou, Li
Li, Siming
Wang, Xuan
Yan, Xieqiao
Kong, Yan
Guo, Jun
author_sort Dai, Jie
collection PubMed
description Purpose: Polymorphisms of genes in the platelet-derived growth factor (PDGF) signaling pathway have been found to predict cutaneous melanoma (CM) survival, but their clinical effects in acral melanoma (AM) patients have not been explored. The aim of this study was to characterize the functional effect of the tag single-nucleotide polymorphism (SNP) rs2228230:C>T and assess its association with clinical outcomes in AM patients. Methods: The effect of rs2228230:C>T on mRNA structures and codon usage values were evaluated using in silico analyses. PDGF receptor alpha (PDGFRA) expression vectors with the rs2228230:C or rs2228230:T allele were constructed to evaluate the expression and signaling activity of PDGFRA. The expression of PDGFRA in AM samples was measured using in situ RNAscope hybridization and immunohistochemical staining. The association of the rs2228230 genotype with survival was analyzed in two independent AM cohorts. Results: In silico analyses indicated that the rs2228230:T allele increases the minimum free energy and reduces synonymous codon usage. The rs2228230:T allele decreased the expression of PDGFRA by reducing the stability of its mRNA and protein as well as the signaling activity of the MAPK and PI3K/AKT pathways. PDGFRA mRNA and protein expression was significantly reduced in AM tissues with the rs2228230:T allele. The progression-free survival and overall survival of AM patients with the rs2228230:T allele were significantly longer than those of patients with the CC genotype. Conclusion: Our study indicated that rs2228230:T can reduce the expression of PDGFRA and downstream signaling activity and is associated with better survival in AM patients.
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spelling pubmed-70862472020-03-27 A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma Dai, Jie Yang, Lu Xu, Tianxiao Si, Lu Cui, Chuanliang Sheng, Xinan Chi, Zhihong Mao, Lili Lian, Bin Tang, Bixia Bai, Xue Zhou, Li Li, Siming Wang, Xuan Yan, Xieqiao Kong, Yan Guo, Jun J Cancer Research Paper Purpose: Polymorphisms of genes in the platelet-derived growth factor (PDGF) signaling pathway have been found to predict cutaneous melanoma (CM) survival, but their clinical effects in acral melanoma (AM) patients have not been explored. The aim of this study was to characterize the functional effect of the tag single-nucleotide polymorphism (SNP) rs2228230:C>T and assess its association with clinical outcomes in AM patients. Methods: The effect of rs2228230:C>T on mRNA structures and codon usage values were evaluated using in silico analyses. PDGF receptor alpha (PDGFRA) expression vectors with the rs2228230:C or rs2228230:T allele were constructed to evaluate the expression and signaling activity of PDGFRA. The expression of PDGFRA in AM samples was measured using in situ RNAscope hybridization and immunohistochemical staining. The association of the rs2228230 genotype with survival was analyzed in two independent AM cohorts. Results: In silico analyses indicated that the rs2228230:T allele increases the minimum free energy and reduces synonymous codon usage. The rs2228230:T allele decreased the expression of PDGFRA by reducing the stability of its mRNA and protein as well as the signaling activity of the MAPK and PI3K/AKT pathways. PDGFRA mRNA and protein expression was significantly reduced in AM tissues with the rs2228230:T allele. The progression-free survival and overall survival of AM patients with the rs2228230:T allele were significantly longer than those of patients with the CC genotype. Conclusion: Our study indicated that rs2228230:T can reduce the expression of PDGFRA and downstream signaling activity and is associated with better survival in AM patients. Ivyspring International Publisher 2020-03-04 /pmc/articles/PMC7086247/ /pubmed/32226509 http://dx.doi.org/10.7150/jca.43010 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Dai, Jie
Yang, Lu
Xu, Tianxiao
Si, Lu
Cui, Chuanliang
Sheng, Xinan
Chi, Zhihong
Mao, Lili
Lian, Bin
Tang, Bixia
Bai, Xue
Zhou, Li
Li, Siming
Wang, Xuan
Yan, Xieqiao
Kong, Yan
Guo, Jun
A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma
title A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma
title_full A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma
title_fullStr A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma
title_full_unstemmed A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma
title_short A Functional Synonymous Variant in PDGFRA Is Associated with Better Survival in Acral Melanoma
title_sort functional synonymous variant in pdgfra is associated with better survival in acral melanoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086247/
https://www.ncbi.nlm.nih.gov/pubmed/32226509
http://dx.doi.org/10.7150/jca.43010
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