Evidence map›Paper›PMID 40699463›Full record

ArticleDiscover oncology2025

A phase separation-related gene signature for prognosis prediction and immunotherapy response evaluation in gastric cancer with targeted natural compound discovery.

Yanjuan Jia, Yuanyuan Ma, Zhenhao Li, Wenze Zhang, Rukun Lu, Wanxia Wang, Chaojun Wei, Chunyan Wei, Yonghong Li, Xiaoling Gao and 1 more

Abstract read
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Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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11 authors.

Yanjuan Jia *NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Donggang West Road 204, Chengguan District, Lanzhou, 730000, Gansu, China.
Yuanyuan Ma *The Second Department of Critical Care Medicine, Xi'an Daxing Hospital, Xi'an, 710000, China.
Zhenhao Li *NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Donggang West Road 204, Chengguan District, Lanzhou, 730000, Gansu, China.
Wenze ZhangThe First School of Clinical Medicine, Lanzhou University, Lanzhou, 730000, China.
Rukun LuThe School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, China.
Wanxia WangNHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Donggang West Road 204, Chengguan District, Lanzhou, 730000, Gansu, China.
Chaojun WeiNHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Donggang West Road 204, Chengguan District, Lanzhou, 730000, Gansu, China.
Chunyan WeiGansu Provincial Hospital, Lanzhou, 730000, China.
Yonghong LiNHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Donggang West Road 204, Chengguan District, Lanzhou, 730000, Gansu, China. Liyonghong-gsph@hotmail.com.
Xiaoling GaoThe Clinical Laboratory Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, 570100, China. gaoxl008@hotmail.com.
Tao QuNHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Donggang West Road 204, Chengguan District, Lanzhou, 730000, Gansu, China. qutao1720@163.com.

Funding

Gansu Provincial Hospital NHCDP2022019, 2020-ZD-17National Natural Science Foundation of China 32060172National Natural Science Foundation of China 8246111265Natural Science Foundation of Gansu Province 23JRRA1279Natural Science Foundation of Gansu Province 23JRRA1281
6 · The paper itself

Abstract

backgroundAberrant phase separation (PS) has emerged as a pivotal pathogenic mechanism in cancer development. However, its prognostic significance and influence on the tumor immune microenvironment in gastric cancer (GC) remain largely unexplored. This study aimed to develop a PS-related risk model for predicting clinical outcomes and immunotherapy response, and to identify potential natural small-molecule compounds targeting proteins within this PS-related network.

methodsWe integrated transcriptomic data from the TCGA-STAD and GSE62254 datasets with four PS-related databases (including DrLLPS, PhaSepDB, PhaSePro, and LLPSDB) to identify candidate signature genes. The prognostic model was developed using least absolute shrinkage and selection operator (LASSO) regression and validated in both cohorts. Immune checkpoint inhibitor (ICI) response between PS-related high- and low-risk groups was evaluated using TIDE algorithm scores. Potential therapeutic agents targeting signature genes were screened via Connectivity Map and HERB database analyses, followed by molecular docking validation.

resultsBy Integrating analysis of the differential expression dataset from TCGA-STAD (n = 407, 375 tumor/32 normal) with prognosis-related dataset and PS-related dataset, we identified 78 candidate genes and developed a robust 21-gene risk prediction model. The model effectively stratified GC patients into high-risk and low-risk subgroups, with consistent performance in the independent GSE62254 validation cohort (n = 300, tumor). Compared to low-risk patients, high-risk patients exhibited poorer survival, a more immunosuppressive microenvironment, and a reduced response to immunotherapy. Moreover, computational screening identified 18 potential therapeutic natural compounds, 13 of which showed high-affinity binding to signature genes (docking scores > 6.0).

conclusionsOur study developed a novel PS-related risk model that predicts GC outcomes, characterizes tumor immune microenvironment, evaluates immunotherapy response, and identifies targeting small molecules. These findings advance the understanding of PS regulation in GC and provide a framework for personalized therapy.

Indexed as

Gastric cancerImmunotherapy responseNatural small moleculesPhase separation

Identifiers

PMID40699463
PMCPMC12287496

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.