Classification of lung adenocarcinoma based on senescence-related genes identifies a cluster with immunotherapy resistance and poor prognosis.

IF 2.9 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Discover. Oncology Pub Date : 2025-03-20 DOI:10.1007/s12672-025-02127-9
Xinrui Gao, Xiang Shen, Shasha Huang, Shangke Huang
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Abstract

Lung adenocarcinoma is one of the major contributors to cancer-related mortality, with immunotherapy emerging as a key treatment. However, many patients exhibit resistance to immune checkpoint inhibitors. Cellular senescence has been linked to tumor progression and drug resistance, influencing the tumor microenvironment. This study applied consensus clustering to classify lung adenocarcinoma patients into two clusters based on senescence-related gene expression, revealing differing immune characteristics. One of the identified clusters exhibited immunosuppressive characteristics and showed resistance to immunotherapy. A senescence-related risk score was developed using machine learning to predict immunotherapy response and prognosis. High senescence-related risk score correlated with poorer survival and increased immunotherapy resistance across multiple cancer types. The senescence-related risk score model showed robust predictive ability in both the training and validation cohorts. These findings suggest a link between senescence and immunotherapy resistance, and further investigation into their relationship could reveal new perspectives for cancer treatment.

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基于衰老相关基因的肺腺癌分类确定了免疫治疗耐药和预后不良的一类。
肺腺癌是导致癌症相关死亡率的主要因素之一,而免疫疗法正成为一种重要的治疗手段。然而,许多患者对免疫检查点抑制剂表现出耐药性。细胞衰老与肿瘤进展和耐药性有关,会影响肿瘤微环境。本研究根据衰老相关基因的表达,应用共识聚类将肺腺癌患者分为两个群组,揭示了不同的免疫特征。其中一个群组表现出免疫抑制特征,对免疫疗法有抵抗力。利用机器学习技术开发了衰老相关风险评分,以预测免疫疗法的反应和预后。在多种癌症类型中,高衰老相关风险评分与较差的生存率和较高的免疫疗法耐药性相关。衰老相关风险评分模型在训练队列和验证队列中都显示出强大的预测能力。这些发现表明衰老与免疫疗法耐药性之间存在联系,进一步研究它们之间的关系可能会为癌症治疗提供新的视角。
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来源期刊
Discover. Oncology
Discover. Oncology Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
2.40
自引率
9.10%
发文量
122
审稿时长
5 weeks
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