Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer

BackgroundGastric cancer (GC) is a malignant tumor with poor prognosis. The diverse patterns of programmed cell death (PCD) are significantly associated with the pathogenesis and progression of GC, and it has the potential to serve as prognostic and drug sensitivity indicators for GC.MethodThe seque...

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Main Authors: Qiying Song, Shihe Liu, Di Wu, Aizhen Cai
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1511453/full
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author Qiying Song
Shihe Liu
Di Wu
Aizhen Cai
author_facet Qiying Song
Shihe Liu
Di Wu
Aizhen Cai
author_sort Qiying Song
collection DOAJ
description BackgroundGastric cancer (GC) is a malignant tumor with poor prognosis. The diverse patterns of programmed cell death (PCD) are significantly associated with the pathogenesis and progression of GC, and it has the potential to serve as prognostic and drug sensitivity indicators for GC.MethodThe sequencing data and clinical characteristics of GC patients were downloaded from The Cancer Genome Atlas and GEO databases. LASSO cox regression method was used to screen feature genes and develop the PCD score (PCDS). Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore immunotherapy response. By integrating PCDS with clinical characteristics, we constructed and validated a nomogram that demonstrated robust predictive performance.ResultsWe screened nine PCD-related genes (SERPINE1, PLPPR4, CDO1, MID2, NOX4, DYNC1I1, PDK4, MYB, TUBB2A) to create the PCDS. We found that GC patients with high PCDS experienced significantly poorer prognoses, and PCDS was identified as an independent prognostic factor. Furthermore, there was a significant difference in immune profile between high PCDS and low PCDS groups. Additionally, drug sensitivity analysis indicated that patients with a high PCDS may exhibit resistance to immunotherapy and standard adjuvant chemotherapy regimens; however, they may benefit from the FDA-approved drug Dasatinib.ConclusionOverall, we confirmed that the PCDS is a prognostic risk factor and a valuable predictor of immunotherapy response in GC patients, which provides new evidence for the potential application of GC.
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spelling doaj-art-103295e35fcd4c5aa88439acd720a4b82025-02-04T06:31:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15114531511453Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancerQiying SongShihe LiuDi WuAizhen CaiBackgroundGastric cancer (GC) is a malignant tumor with poor prognosis. The diverse patterns of programmed cell death (PCD) are significantly associated with the pathogenesis and progression of GC, and it has the potential to serve as prognostic and drug sensitivity indicators for GC.MethodThe sequencing data and clinical characteristics of GC patients were downloaded from The Cancer Genome Atlas and GEO databases. LASSO cox regression method was used to screen feature genes and develop the PCD score (PCDS). Immune cell infiltration, immune checkpoint expression, Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and drug sensitivity analysis were used to explore immunotherapy response. By integrating PCDS with clinical characteristics, we constructed and validated a nomogram that demonstrated robust predictive performance.ResultsWe screened nine PCD-related genes (SERPINE1, PLPPR4, CDO1, MID2, NOX4, DYNC1I1, PDK4, MYB, TUBB2A) to create the PCDS. We found that GC patients with high PCDS experienced significantly poorer prognoses, and PCDS was identified as an independent prognostic factor. Furthermore, there was a significant difference in immune profile between high PCDS and low PCDS groups. Additionally, drug sensitivity analysis indicated that patients with a high PCDS may exhibit resistance to immunotherapy and standard adjuvant chemotherapy regimens; however, they may benefit from the FDA-approved drug Dasatinib.ConclusionOverall, we confirmed that the PCDS is a prognostic risk factor and a valuable predictor of immunotherapy response in GC patients, which provides new evidence for the potential application of GC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1511453/fullgastric cancerprogram cell deathprognosisimmunotherapydrug sensitivity
spellingShingle Qiying Song
Shihe Liu
Di Wu
Aizhen Cai
Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
Frontiers in Immunology
gastric cancer
program cell death
prognosis
immunotherapy
drug sensitivity
title Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
title_full Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
title_fullStr Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
title_full_unstemmed Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
title_short Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
title_sort multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer
topic gastric cancer
program cell death
prognosis
immunotherapy
drug sensitivity
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1511453/full
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AT shiheliu multipleprogrammedcelldeathpatternspredicttheprognosisanddrugsensitivityingastriccancer
AT diwu multipleprogrammedcelldeathpatternspredicttheprognosisanddrugsensitivityingastriccancer
AT aizhencai multipleprogrammedcelldeathpatternspredicttheprognosisanddrugsensitivityingastriccancer