Characterization of prognostic signature related with twelve types of programmed cell death in lung squamous cell carcinoma.

IF 1.5 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS Journal of Cardiothoracic Surgery Pub Date : 2024-10-01 DOI:10.1186/s13019-024-03039-5
Saiyu Li, Bing Ding, Duanli Weng
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Abstract

Objective: This study aimed to develop a prognostic cell death index (CDI) based on the expression of genes related with various types of programmed cell death (PCD), and to assess its clinical relevance in lung squamous cell carcinoma (LUSC).

Methods: PCD-related genes were gathered and analyzed in silico using the transcriptomic data from the LUSC cohorts of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Differentially expressed PCD genes were analyzed, and a prognostic model was subsequently constructed. CDI scores were calculated for each patient, and their correlations with clinical features, survival outcomes, tumor mutation burden, gene clusters, and tumor microenvironment were investigated. Unsupervised consensus clustering was performed based on CDI model genes. Furthermore, the correlation of CDI for sensitivity of targeted drugs, chemotherapy efficacy, and immunotherapy responses was assessed.

Results: Based on 351 differentially expressed PCD genes in LUSC, a CDI signature comprising FGA, GAB2, JUN, and CDKN2A was identified. High CDI scores were significantly associated with poor survival outcomes (p < 0.05). Unsupervised clustering revealed three distinct patient subsets with varying survival rates. CDKN2A exhibited significantly different mutation patterns between patients with high and low CDI scores (p < 0.01). High CDI scores were also linked to increased immune cell infiltration of specific subsets and altered expression of immune-related genes. Patients with high-CDI showed reduced sensitivity to several chemotherapeutic drugs and a higher Tumor Immune Dysfunction and Exclusion (TIDE) score, indicating potential resistance to immunotherapy.

Conclusion: The CDI signature based on PCD genes offers valuable prognostic insights into LUSC, reflecting molecular heterogeneity, immune microenvironment associations, and potential therapeutic challenges. The CDI holds potential clinical utility in predicting treatment responses and guiding the selection of appropriate therapies for patients with LUSC. Future studies are warranted to further validate the prognostic value of CDI in combination with clinical factors and to explore its application across diverse patient cohorts.

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与肺鳞癌十二种程序性细胞死亡相关的预后特征描述
研究目的本研究旨在根据各种类型程序性细胞死亡(PCD)相关基因的表达建立预后细胞死亡指数(CDI),并评估其在肺鳞癌(LUSC)中的临床意义:方法:利用癌症基因组图谱(TCGA)和临床肿瘤蛋白质组分析联盟(CPTAC)的肺鳞癌队列中的转录组数据,收集与PCD相关的基因并进行硅分析。对差异表达的 PCD 基因进行了分析,随后构建了预后模型。计算了每位患者的 CDI 分数,并研究了它们与临床特征、生存结果、肿瘤突变负荷、基因簇和肿瘤微环境的相关性。根据 CDI 模型基因进行了无监督共识聚类。此外,还评估了CDI与靶向药物敏感性、化疗疗效和免疫疗法反应的相关性:结果:基于LUSC中351个差异表达的PCD基因,确定了由FGA、GAB2、JUN和CDKN2A组成的CDI特征。高 CDI 评分与不良生存预后显著相关(p 结论:基于 PCD 基因的 CDI 特征与不良生存预后显著相关:基于 PCD 基因的 CDI 特征为 LUSC 的预后提供了有价值的见解,反映了分子异质性、免疫微环境关联和潜在的治疗挑战。CDI 在预测治疗反应和指导 LUSC 患者选择适当疗法方面具有潜在的临床实用性。未来的研究需要进一步验证 CDI 与临床因素相结合的预后价值,并探索其在不同患者队列中的应用。
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来源期刊
Journal of Cardiothoracic Surgery
Journal of Cardiothoracic Surgery 医学-心血管系统
CiteScore
2.50
自引率
6.20%
发文量
286
审稿时长
4-8 weeks
期刊介绍: Journal of Cardiothoracic Surgery is an open access journal that encompasses all aspects of research in the field of Cardiology, and Cardiothoracic and Vascular Surgery. The journal publishes original scientific research documenting clinical and experimental advances in cardiac, vascular and thoracic surgery, and related fields. Topics of interest include surgical techniques, survival rates, surgical complications and their outcomes; along with basic sciences, pediatric conditions, transplantations and clinical trials. Journal of Cardiothoracic Surgery is of interest to cardiothoracic and vascular surgeons, cardiothoracic anaesthesiologists, cardiologists, chest physicians, and allied health professionals.
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