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弥漫大 B 细胞淋巴瘤中新型免疫原性 PANoptosis 相关基因特征的整合分析及其预后评估与治疗决策价值

英文原题:Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making.

查看英文原题

Integrative analysis of a novel immunogenic PANoptosis‑related gene signature in diffuse large B-cell lymphoma for prognostication and therapeutic decision-making.

PubMed 2024/12/05(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

本研究旨在开发泛凋亡(PANoptosis)相关基因预后指数(PANGPI),评估其预测弥漫性大B细胞淋巴瘤(DLBCL)患者预后及免疫治疗应答的潜在价值。研究分析了GEO数据库中的DLBCL差异表达基因,并映射至PANoptosis基因集。通过LASSO Cox回归和多变量Cox回归评估PANGPI特征的独立预后价值。

此外,评估了两种亚组的TIL(肿瘤浸润淋巴细胞)特征和突变图谱,并使用GDSC数据库预测药物敏感性。研究还进行了计算机模拟对接和分子动力学模拟,以阐明所预测药物的相互作用方式。PANGPI风险评分是DLBCL患者预后的独立危险因素,且具有良好的预后预测效能。

此外,TIL细胞毒活性与PANGPI评分呈正相关。PANGPI还帮助为高危DLBCL患者筛选出3种化疗药物,包括BMS-536924、吉非替尼和Navitoclax。

本研究建立了一种新的DLBCL泛凋亡相关基因分型系统,可为开发DLBCL新型生物标志物提供新思路。

展开英文摘要原文

This study aimed to develop a PANoptosis-related gene prognostic index (PANGPI) to explore its potential value in predicting the prognosis and immunotherapy response of diffuse large B-cell lymphoma (DLBCL). Differentially expressed genes of DLBCL from GEO databases were analyzed and mapped to the PANoptosis gene set. The independent prognostic value of the PANGPI signature was evaluated using LASSO Cox regression and multivariate Cox regression.

Additionally, the tumor infiltrating lymphocyte (TIL) characteristics and mutation landscape of both subgroups were evaluated, and drug sensitivity was predicted using the GDSC database.

Furthermore, in silico docking and molecular dynamic simulation studies were presented to elucidate the mode of interaction of these predicted drugs. The PANGPI risk score was an independent risk factor for the prognosis of patients with DLBCL and exhibited good prognostic predictive performance.

Furthermore, the cytolytic activity of the TILs was positively correlated with the PANGPI scores.

Additionally, the PANGPI enabled the identification of 3 chemotherapeutic agents, including BMS-536924, Gefitinib, Navitoclax for DLBCL patients in the high-risk group.

We established a novel PANoptosis-related gene subtyping system in DLBCL, which could shed a novel light on the development of new biomarkers for DLBCL.

论文信息

作者
Xu M、Ruan M、Zhu W、Xu J、Lin L、Li W、Zhu W
第一作者单位
Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.China
通讯作者单位
Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. willonzhu@163.com.China
期刊
Scientific reports2024 Dec 5
原文标识
PubMed 39639038 · DOI 10.1038/s41598-024-81420-z