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Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma
BACKGROUND: In recent years, there has been growing evidence indicating a relationship between liquid–liquid phase separation (LLPS) and cancer development. However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidat...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150491/ https://www.ncbi.nlm.nih.gov/pubmed/37127623 http://dx.doi.org/10.1186/s12885-023-10847-w |
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author | Liu, Jianlan Pei, Shengbin Zhang, Pengpeng Jiang, Keyu Luo, Binlin Hou, Zuoqiong Yao, Gang Tang, Jian |
author_facet | Liu, Jianlan Pei, Shengbin Zhang, Pengpeng Jiang, Keyu Luo, Binlin Hou, Zuoqiong Yao, Gang Tang, Jian |
author_sort | Liu, Jianlan |
collection | PubMed |
description | BACKGROUND: In recent years, there has been growing evidence indicating a relationship between liquid–liquid phase separation (LLPS) and cancer development. However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidated. In the current study, the impact of LLPS-related genes on melanoma prognosis has been explored. METHODS: LLPS-related genes were retrieved from the DrLLPS database. The prognostic feature for LLPS in melanoma was developed in The Cancer Genome Atlas (TCGA) dataset and verified in the GSE65904 cohort. Based on risk scores, melanoma patients were categorized into high- and low-risk groups. Thereafter, the differences in clinicopathological correlation, functional enrichment, immune landscape, tumor mutational burden, and impact of immunotherapy between the two groups were investigated. Finally, the role of key gene TROAP in melanoma was validated by in vitro and in vivo experiments. RESULTS: The LLPS-related gene signature was developed based on MLKL, PARVA, PKP1, PSME1, RNF114, and TROAP. The risk score was a crucial independent prognostic factor for melanoma and patients with high-risk scores were related to a worse prognosis. Approximately, all immune-relevant characteristics, such as immune cell infiltration and immune scores, were extremely evident in patients with low-risk scores. The findings from the in vitro and in vivo experiments indicated that the viability, proliferation, and invasion ability of melanoma cells were drastically decreased after the knockdown of TROAP. CONCLUSION: Our gene signature can independently predict the survival of melanoma patients. It provides a basis for the exploration of the relationship between LLPS and melanoma and can offer a fresh perspective on the clinical diagnosis and treatment of the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10847-w. |
format | Online Article Text |
id | pubmed-10150491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101504912023-05-02 Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma Liu, Jianlan Pei, Shengbin Zhang, Pengpeng Jiang, Keyu Luo, Binlin Hou, Zuoqiong Yao, Gang Tang, Jian BMC Cancer Research BACKGROUND: In recent years, there has been growing evidence indicating a relationship between liquid–liquid phase separation (LLPS) and cancer development. However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidated. In the current study, the impact of LLPS-related genes on melanoma prognosis has been explored. METHODS: LLPS-related genes were retrieved from the DrLLPS database. The prognostic feature for LLPS in melanoma was developed in The Cancer Genome Atlas (TCGA) dataset and verified in the GSE65904 cohort. Based on risk scores, melanoma patients were categorized into high- and low-risk groups. Thereafter, the differences in clinicopathological correlation, functional enrichment, immune landscape, tumor mutational burden, and impact of immunotherapy between the two groups were investigated. Finally, the role of key gene TROAP in melanoma was validated by in vitro and in vivo experiments. RESULTS: The LLPS-related gene signature was developed based on MLKL, PARVA, PKP1, PSME1, RNF114, and TROAP. The risk score was a crucial independent prognostic factor for melanoma and patients with high-risk scores were related to a worse prognosis. Approximately, all immune-relevant characteristics, such as immune cell infiltration and immune scores, were extremely evident in patients with low-risk scores. The findings from the in vitro and in vivo experiments indicated that the viability, proliferation, and invasion ability of melanoma cells were drastically decreased after the knockdown of TROAP. CONCLUSION: Our gene signature can independently predict the survival of melanoma patients. It provides a basis for the exploration of the relationship between LLPS and melanoma and can offer a fresh perspective on the clinical diagnosis and treatment of the disease. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10847-w. BioMed Central 2023-05-01 /pmc/articles/PMC10150491/ /pubmed/37127623 http://dx.doi.org/10.1186/s12885-023-10847-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Liu, Jianlan Pei, Shengbin Zhang, Pengpeng Jiang, Keyu Luo, Binlin Hou, Zuoqiong Yao, Gang Tang, Jian Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
title | Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
title_full | Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
title_fullStr | Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
title_full_unstemmed | Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
title_short | Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
title_sort | liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10150491/ https://www.ncbi.nlm.nih.gov/pubmed/37127623 http://dx.doi.org/10.1186/s12885-023-10847-w |
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