mpt驱动的坏死相关基因标记在胃癌中的预测意义及其对肿瘤微环境的影响。

IF 2.8 3区 医学 Q2 ONCOLOGY Clinical & Translational Oncology Pub Date : 2024-12-17 DOI:10.1007/s12094-024-03832-7
Silan Huang, Lingli Huang, Qi Jiang, Chang Jiang, Guifang Guo
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引用次数: 0

摘要

背景:胃癌(GC)提出了重大的管理挑战。mpt驱动性坏死(MPTDN)在各种情况下都起着重要作用,但其与GC的关系尚不清楚。本研究旨在探讨mptdn相关基因(MPTDNRGs)在胃癌中的预测意义及其对肿瘤免疫微环境(TIME)的影响。方法:GC的RNA测序数据来源于TCGA和GEO数据库。评估肿瘤和正常样本的突变谱和MPTDNRG的表达。使用单变量Cox回归和LASSO回归确定预后mrna。根据风险评分将GC患者分为高危组和低危组,进行生存分析,评价MPTDN评分与临床病理特征、功能通路、TIME、免疫治疗反应的相关性。结果:MPTDNRGs在GC中的突变率为64%,其中22个表达差异显著。单因素Cox和LASSO回归确定了15个独立预后的MPTDNRGs。预后风险模型将患者分为两组,揭示了总生存期和无病生存期的显著差异。结合特征和临床特征的nomogram预测预后具有很强的特异性和敏感性。MPTDN评分与临床特征、功能通路和时间显著相关。scRNA-seq分析显示,mptdn特征在CD8 + T细胞、恶性细胞和肌成纤维细胞中表达较高。TIDE分析表明,高风险患者对免疫治疗的反应较低,而低风险患者可能受益更多。重要的是,使用尿路上皮癌数据的验证证实了免疫治疗对低风险患者有更好的预后。结论:本研究强调了mptdn相关特征在预测胃癌预后和指导治疗决策中的重要性。
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Predictive significance of MPT-driven necrosis-related genes signature in gastric cancer and their impact on the tumor microenvironment.

Background: Gastric cancer (GC) presents significant management challenges. MPT-driven necrosis (MPTDN) plays a significant role in various conditions, but its connection with GC is unclear. This study aimed to investigate the predictive significance of MPTDN-related genes (MPTDNRGs) in GC and their effect on the tumor immune microenvironment (TIME).

Methods: RNA sequencing data for GC were sourced from TCGA and GEO databases. The mutation profiles and MPTDNRG expression between tumor and normal samples were assessed. Prognostic mRNAs were identified using univariate Cox regression and LASSO regression. GC patients were classified into high- and low-risk groups according to risk scores, followed by survival analysis and evaluation of correlations between MPTDN score and clinicopathological features, functional pathway, TIME, and responses to immunotherapy.

Results: MPTDNRGs exhibited a 64% mutation rate in GC, with 22 showing significant expression differences. Univariate Cox and LASSO regression identified 15 independently prognostic MPTDNRGs. The prognostic risk model stratified patients into two groups, revealing significant differences in overall and disease-free survival. A nomogram incorporating the signature and clinical characteristics showed strong specificity and sensitivity in predicting prognosis. The MPTDN score was significantly associated with clinical characteristics, functional pathways, and TIME. scRNA-seq analysis indicated higher MPTDN-signature expression in CD8 + T cells, malignant cells, and myofibroblasts. TIDE analysis suggested high-risk patients have reduced responses to immunotherapy, while low-risk patients could benefit more. Importantly, validation using urothelial carcinoma data confirmed a better prognosis for low-risk patients with immunotherapy.

Conclusion: This study highlights the importance of MPTDN-related signatures in predicting GC prognosis and guiding therapeutic decisions.

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来源期刊
CiteScore
6.20
自引率
2.90%
发文量
240
审稿时长
1 months
期刊介绍: Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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