Liu Donghui, Liu Mingzhu, Du Juan
Department of Intervention, Jilin Cancer Hospital, Changchun, Jilin, China.
Department of Second Internal Medicine, Jilin Cancer Hospital, No. 1018, Huguang Road, Chaoyang District, Changchun, 130012, Jilin, China.
Discov Oncol. 2025 May 30;16(1):963. doi: 10.1007/s12672-025-02804-9.
Liquid-liquid phase separation (LLPS) is the membrane-less formation of functional assemblies from specific molecules. It plays a key role in tumor growth by governing gene expression. This study aims to identify LLPS-associated molecular subtypes and prognostic biomarkers in gastric cancer (GC).
LLPS-associated genes, gene expression profiles and clinical data for GC were sourced from public databases. Differential expression analysis, UpSetR package, and Cox regression analyses were employed to pinpoint LLPS-related biomarkers. Consensus clustering was employed to confirm GC molecular subtypes. Mendelian randomization (MR) was applied to uncover causal links between biomarkers and GC risk. The quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) gauged biomarker expression in GC cells (BGC-823, MGC-803, and MKN-45) and normal gastric epithelial cells (GES-1).
Totally 62 LLPS-associated genes were detected. Subsequently, three LLPS-associated subtypes of GC were confirmed, containing subtypes 1, 2 and 3, and patients in subtype 2 had significantly worse overall survival (OS) than subtypes 1 and 3. Furthermore, three LLPS-associated biomarkers (DACT1, PTPN6, and GLE1) were identified for prognostic model construction. Kaplan-Meier (KM) curve suggested that OS was significantly shorter in low-expression of GLE1 and PTPN6 groups than in high-expression groups, respectively, while an opposite trend was observed in DACT1. Notably, MR analysis suggested that DACT1 was associated with the risk of GC. Moreover, qRT-PCR results demonstrated that PTPN6 and GLE1 were significantly higher expressed in GC cell lines compared to GSE-1 cells, whereas the opposite was true for DACT1.
This work detected three LLPS-associated prognostic biomarkers (DACT1, PTPN6, and GLE1) for GC. These findings were expected to lead to the development of more precise and effective therapeutic strategies for GC in the future.
液-液相分离（LLPS）是特定分子形成无膜功能聚集体的过程。它通过调控基因表达在肿瘤生长中起关键作用。本研究旨在识别胃癌（GC）中与LLPS相关的分子亚型和预后生物标志物。
从公共数据库获取GC的LLPS相关基因、基因表达谱和临床数据。采用差异表达分析、UpSetR软件包和Cox回归分析来确定LLPS相关生物标志物。运用一致性聚类来确认GC分子亚型。采用孟德尔随机化（MR）来揭示生物标志物与GC风险之间的因果关系。定量逆转录聚合酶链反应（qRT-PCR）检测GC细胞（BGC-823、MGC-803和MKN-45）和正常胃上皮细胞（GES-1）中生物标志物的表达。
共检测到62个LLPS相关基因。随后，确认了GC的三种LLPS相关亚型，即亚型1、2和3，其中亚型2患者的总生存期（OS）明显差于亚型1和3。此外，确定了三种LLPS相关生物标志物（DACT1、PTPN6和GLE1）用于构建预后模型。Kaplan-Meier（KM）曲线表明，GLE1和PTPN6低表达组的OS分别明显短于高表达组，而DACT1则呈现相反趋势。值得注意的是，MR分析表明DACT1与GC风险相关。此外，qRT-PCR结果显示，与GSE-1细胞相比，PTPN6和GLE1在GC细胞系中表达明显更高，而DACT1则相反。
本研究发现了三种GC的LLPS相关预后生物标志物（DACT1、PTPN6和GLE1）。这些发现有望在未来推动针对GC的更精确有效的治疗策略的发展。
