Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer
AimProgrammed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.Method...
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| Language: | English |
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1477363/full |
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| author | Feizhi Lin Xiaojiang Chen Chengcai Liang Ruopeng Zhang Guoming Chen Ziqi Zheng Bowen Huang Chengzhi Wei Zhoukai Zhao Feiyang Zhang Zewei Chen Shenghang Ruan Yongming Chen Runcong Nie Yuangfang Li Baiwei Zhao |
| author_facet | Feizhi Lin Xiaojiang Chen Chengcai Liang Ruopeng Zhang Guoming Chen Ziqi Zheng Bowen Huang Chengzhi Wei Zhoukai Zhao Feiyang Zhang Zewei Chen Shenghang Ruan Yongming Chen Runcong Nie Yuangfang Li Baiwei Zhao |
| author_sort | Feizhi Lin |
| collection | DOAJ |
| description | AimProgrammed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.MethodsWe analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 were used for validation. Single-cell transcriptome data from GSE183904 were analyzed to explore the relationship between TME and the newly constructed model, named PCD index (PCDI). Drug sensitivity comparisons were made between patients with high and low PCDI scores.ResultsWe developed a novel twelve-gene signature called PCDI. Upon validation, GC patients with higher PCDI scores had poorer prognoses. A high-performance nomogram integrating the PCDI with clinical features was also established. Additionally, single-cell transcriptome data analysis suggested that PCDI might be linked to critical components of the TME. Patients with high PCDI scores exhibited resistance to standard adjuvant chemotherapy and immunotherapy but might benefit from targeted treatments with NU7441, Dasatinib, and JQ1.ConclusionThe novel PCDI model shows significant potential in predicting clinical prognosis and drug sensitivity of GC, thereby facilitating personalized treatment strategies for patients with GC. |
| format | Article |
| id | doaj-art-979c62aa565d453e962a11ef4e19886c |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-979c62aa565d453e962a11ef4e19886c2025-08-20T02:37:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-12-011510.3389/fphar.2024.14773631477363Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancerFeizhi LinXiaojiang ChenChengcai LiangRuopeng ZhangGuoming ChenZiqi ZhengBowen HuangChengzhi WeiZhoukai ZhaoFeiyang ZhangZewei ChenShenghang RuanYongming ChenRuncong NieYuangfang LiBaiwei ZhaoAimProgrammed cell death (PCD) critically influences the tumor microenvironment (TME) and is intricately linked to tumor progression and patient prognosis. This study aimed to develop a novel prognostic indicator and marker of drug sensitivity in patients with gastric cancer (GC) based on PCD.MethodsWe analyzed genes associated with 14 distinct PCD patterns using bulk transcriptome data and clinical information from TCGA-STAD for model construction with univariate Cox regression and LASSO regression analyses. Microarray data from GSE62254, GSE15459, and GSE26901 were used for validation. Single-cell transcriptome data from GSE183904 were analyzed to explore the relationship between TME and the newly constructed model, named PCD index (PCDI). Drug sensitivity comparisons were made between patients with high and low PCDI scores.ResultsWe developed a novel twelve-gene signature called PCDI. Upon validation, GC patients with higher PCDI scores had poorer prognoses. A high-performance nomogram integrating the PCDI with clinical features was also established. Additionally, single-cell transcriptome data analysis suggested that PCDI might be linked to critical components of the TME. Patients with high PCDI scores exhibited resistance to standard adjuvant chemotherapy and immunotherapy but might benefit from targeted treatments with NU7441, Dasatinib, and JQ1.ConclusionThe novel PCDI model shows significant potential in predicting clinical prognosis and drug sensitivity of GC, thereby facilitating personalized treatment strategies for patients with GC.https://www.frontiersin.org/articles/10.3389/fphar.2024.1477363/fullgastric cancerprogrammed cell deathprognostic modeldrug sensitivitytumor microenvironment |
| spellingShingle | Feizhi Lin Xiaojiang Chen Chengcai Liang Ruopeng Zhang Guoming Chen Ziqi Zheng Bowen Huang Chengzhi Wei Zhoukai Zhao Feiyang Zhang Zewei Chen Shenghang Ruan Yongming Chen Runcong Nie Yuangfang Li Baiwei Zhao Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer Frontiers in Pharmacology gastric cancer programmed cell death prognostic model drug sensitivity tumor microenvironment |
| title | Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer |
| title_full | Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer |
| title_fullStr | Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer |
| title_full_unstemmed | Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer |
| title_short | Development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer |
| title_sort | development and validation of a programmed cell death index to predict the prognosis and drug sensitivity of gastric cancer |
| topic | gastric cancer programmed cell death prognostic model drug sensitivity tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1477363/full |
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