Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma

Abstract Background Disulfidptosis, a newly discovered form of cell death resulting from disulfide stress, remains unclear in its role in stomach adenocarcinoma (STAD). This study aimed to establish a novel disulfidptosis and cuproptosis-related lncRNAs (DCRLs) signature for STAD. Methods We sourced...

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Main Authors: Caihao Qu, Xin Yan, Futian Tang, Yumin Li
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-01969-7
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author Caihao Qu
Xin Yan
Futian Tang
Yumin Li
author_facet Caihao Qu
Xin Yan
Futian Tang
Yumin Li
author_sort Caihao Qu
collection DOAJ
description Abstract Background Disulfidptosis, a newly discovered form of cell death resulting from disulfide stress, remains unclear in its role in stomach adenocarcinoma (STAD). This study aimed to establish a novel disulfidptosis and cuproptosis-related lncRNAs (DCRLs) signature for STAD. Methods We sourced RNA-seq data for STAD from the The Cancer Genome Atlas (TCGA) repository. STAD samples underwent nonnegative matrix factorization (NMF) clustering to identify distinct molecular subgroups, followed by Lasso-Cox regression to construct a prognostic model for DCRLs. Subsequently, the model’s clinical predictive capacity was evaluated using a nomogram. The expression of risk lncRNAs was validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results The samples were classified into three molecular subtypes based on DCRLs, with the C1 subtype demonstrating the worst prognosis. We identified four independent prognostic lncRNAs (AC016394.2, NUTM2A-AS1, OIP5-AS1, and LIMS1-AS1) and constructed a prognostic risk model. Survival analysis revealed that high-risk patients had a poorer prognosis. The model’s risk score was strongly correlated with the tumor mutational burden (TMB), microsatellite instability (MSI), immune subtypes, and tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME). Analysis utilizing the Tumor Immune Dysfunction and Exclusion (TIDE) revealed a higher risk of tumor immune evasion among high-risk patients. Moreover, the expression levels of four risk lncRNAs were higher in the majority of gastric cancer cell lines compared to normal cell lines. Conclusion Our study establishes a risk model that effectively predicts clinical outcomes and immune response in STAD.
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spelling doaj-art-08d8294b2e574fc591becc4493fa66a22025-08-20T02:01:38ZengSpringerDiscover Oncology2730-60112025-02-0116111610.1007/s12672-025-01969-7Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinomaCaihao Qu0Xin Yan1Futian Tang2Yumin Li3Lanzhou University Second HospitalLanzhou University Second HospitalLanzhou University Second HospitalLanzhou University Second HospitalAbstract Background Disulfidptosis, a newly discovered form of cell death resulting from disulfide stress, remains unclear in its role in stomach adenocarcinoma (STAD). This study aimed to establish a novel disulfidptosis and cuproptosis-related lncRNAs (DCRLs) signature for STAD. Methods We sourced RNA-seq data for STAD from the The Cancer Genome Atlas (TCGA) repository. STAD samples underwent nonnegative matrix factorization (NMF) clustering to identify distinct molecular subgroups, followed by Lasso-Cox regression to construct a prognostic model for DCRLs. Subsequently, the model’s clinical predictive capacity was evaluated using a nomogram. The expression of risk lncRNAs was validated via quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results The samples were classified into three molecular subtypes based on DCRLs, with the C1 subtype demonstrating the worst prognosis. We identified four independent prognostic lncRNAs (AC016394.2, NUTM2A-AS1, OIP5-AS1, and LIMS1-AS1) and constructed a prognostic risk model. Survival analysis revealed that high-risk patients had a poorer prognosis. The model’s risk score was strongly correlated with the tumor mutational burden (TMB), microsatellite instability (MSI), immune subtypes, and tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME). Analysis utilizing the Tumor Immune Dysfunction and Exclusion (TIDE) revealed a higher risk of tumor immune evasion among high-risk patients. Moreover, the expression levels of four risk lncRNAs were higher in the majority of gastric cancer cell lines compared to normal cell lines. Conclusion Our study establishes a risk model that effectively predicts clinical outcomes and immune response in STAD.https://doi.org/10.1007/s12672-025-01969-7DisulfidptosisCuproptosisClinical outcomesImmune infiltrationNMFStomach adenocarcinoma
spellingShingle Caihao Qu
Xin Yan
Futian Tang
Yumin Li
Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
Discover Oncology
Disulfidptosis
Cuproptosis
Clinical outcomes
Immune infiltration
NMF
Stomach adenocarcinoma
title Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
title_full Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
title_fullStr Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
title_full_unstemmed Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
title_short Construction of a novel disulfidptosis and cuproptosis-related lncRNA signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
title_sort construction of a novel disulfidptosis and cuproptosis related lncrna signature for predicting the clinical outcome and immune response in stomach adenocarcinoma
topic Disulfidptosis
Cuproptosis
Clinical outcomes
Immune infiltration
NMF
Stomach adenocarcinoma
url https://doi.org/10.1007/s12672-025-01969-7
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