Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Jianlan, Pei, Shengbin, Zhang, Pengpeng, Jiang, Keyu, Luo, Binlin, Hou, Zuoqiong, Yao, Gang, Tang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
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
_version_ 1785035370429153280
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
work_keys_str_mv AT liujianlan liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT peishengbin liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT zhangpengpeng liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT jiangkeyu liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT luobinlin liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT houzuoqiong liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT yaogang liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma
AT tangjian liquidliquidphaseseparationthrowsnovelinsightsintotreatmentstrategiesforskincutaneousmelanoma