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肺腺癌中三级淋巴结构相关基因的多组学分析和实验验证:分子亚群、免疫浸润及预后意义

英文原题:Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma.

查看英文原题

Multi-omics profiling and experimental verification of tertiary lymphoid structure-related genes: molecular subgroups, immune infiltration, and prognostic implications in lung adenocarcinoma.

PubMed 2024/09/19(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

肺腺癌(LUAD)以5年生存率低为特征,是最常见且侵袭性最强的肺癌类型。近期研究表明,类似于淋巴结构的三级淋巴结构(TLS)与免疫应答和肿瘤预后密切相关。三级淋巴结构相关基因(TLS-RGs)在肿瘤微环境(TME)中的功能尚不清楚。基于公开数据,我们对TLS-RGs在LUAD中的功能进行了全面研究。首先,我们将LUAD患者分为两个TLS亚型和两个基因亚型。随后,计算风险评分,并使用七个基因(CIITA、FCRL2、GBP1、BIRC3、SCGB1A1、CLDN18和S100P)构建预后模型。为增强TLS评分的临床应用,我们开发了一个精确的列线图。

此外,发现药物敏感性、肿瘤突变负荷(TMB)和癌症干细胞(CSC)指数与TLS评分显著相关。单细胞测序结果反映了TLS-RGs在细胞中的分布。

最后,我们取总生存期(OS)、疾病特异性生存期(DSS)和无进展间期(PFI)预后相关基因的交集,然后通过qRT-PCR进一步验证这些基因的表达。

我们对LUAD中TLS-RGs的深入探究揭示了它们在临床病理特征、预后和TME特征中的可能贡献。这些发现强调了TLS-RGs作为LUAD预后生物标志物和治疗靶点的潜力,从而为个性化治疗策略铺平了道路。

展开英文摘要原文

Lung adenocarcinoma (LUAD), characterized by a low 5-year survival rate, is the most common and aggressive type of lung cancer. Recent studies have shown that tertiary lymphoid structures (TLS), which resemble lymphoid structures, are closely linked to the immune response and tumor prognosis. The functions of the tertiary lymphoid structure-related genes (TLS-RGs) in the tumor microenvironment (TME) are poorly understood.

Based on publicly available data, we conducted a comprehensive study of the function of TLS-RGs in LUAD. Initially, we categorized LUAD patients into two TLS and two gene subtypes. Subsequently, risk scores were calculated, and prognostic models were constructed using seven genes (CIITA, FCRL2, GBP1, BIRC3, SCGB1A1, CLDN18, and S100P). To enhance the clinical application of TLS scores, we have developed a precise nomogram.

Furthermore, drug sensitivity, tumor mutational burden (TMB), and the cancer stem cell (CSC) index were found to be substantially correlated with the TLS scores. Single-cell sequencing results reflected the distribution of TLS-RGs in cells.

Finally, we took the intersection of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) prognosis-related genes and then further validated the expression of these genes by qRT-PCR.

Our in-depth investigation of TLS-RGs in LUAD revealed their possible contributions to the clinicopathological features, prognosis, and characteristics of TME.

These findings underscore the potential of TLS-RGs as prognostic biomarkers and therapeutic targets for LUAD, thereby paving the way for personalized treatment strategies.

论文信息

作者
Wu S、Pan J、Pan Q、Zeng L、Liang R、Li Y
单位
Department of Oncology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, China.China
期刊
Frontiers in immunology2024
原文标识
PubMed 39364403 · DOI 10.3389/fimmu.2024.1453220