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基于集落刺激因子相关基因开发三阴性乳腺癌的预后模型

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目的 三阴性乳腺癌(TNBC)是目前预后最差的乳腺癌亚型,并且缺乏有效的治疗靶点。集落刺激因子(CSFs)是一类能调节血细胞生成和刺激免疫细胞生长发育的细胞因子,在TNBC的恶性进展中发挥重要作用。本文旨在根据集落刺激因子相关基因(CRGs)的表达情况,构建一种新的预后模型,并且分析TNBC对免疫治疗和药物治疗的敏感性。方法 从公共数据库中下载CRGs,在TCGA-BRCA数据库中筛选在正常和TNBC组织中表达差异的CRGs。通LASSO Cox回归分析确定用于构建模型的差异基因并建立CRGs风险评分(CRRS)。进一步在高低风险组中分析了 CRRS与患者预后、临床特征、肿瘤微环境之间的相关性,并评估了CRRS与免疫治疗和药物敏感性之间的关系。结果 鉴定了 842个在TNBC患者乳腺癌组织中存在表达差异的CRGs,并确立了 13个CRGs用于构建预后模型。Kaplan-Meier生存曲线、时间依赖性受试者工作特征曲线等证实了高CRRS的TNBC患者总生存期更短,并且在GEO数据库中进一步证实了 CRRS预后模型的预测能力。结合临床特征的列线图证实CRRS是TNBC患者预后的独立因素。并且高风险组患者肿瘤微环境中免疫浸润水平较低,对部分化疗药物敏感。结论 本文开发了由13个DEGs组成的CRRS模型,该模型可能成为预测TNBC患者预后和指导临床治疗的有用工具,并且其中的关键基因可能是未来治疗的潜在分子靶标。
A Prognostic Model Based on Colony Stimulating Factors-related Genes in Triple-negative Breast Cancer
Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.

triple-negative breast cancercolony stimulating factorsprognostic modeltumor microenvironmentdrug sensitivity

郭雨轩、王智禹、肖沛瑶、郑婵娟、付淑君、贺光春、龙俊、汪婕、邓锡云、王忆安

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湖南师范大学医学院,模式动物与干细胞生物学湖南省重点实验室,长沙 410013

深圳大学材料科学与工程学院,深圳市能源电催化材料重点实验室,深圳市高分子科学与技术重点实验室,广东省新能源材料服务安全重点实验室,深圳 518055

福建医科大学基础医学院肿瘤研究所病理学系及诊断病理中心,福州 350122

湖南省生殖与转化医学工程技术研究中心,长沙 410013

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三阴性乳腺癌 集落刺激因子 预后模型 肿瘤微环境 药物敏感性

2024

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子:0.476
ISSN:1000-3282
年,卷(期):2024.51(10)