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通过大规模转录组数据分析表征乳腺癌与甲状腺癌中的乳酸代谢评分以辅助免疫治疗

英文原题:Characterization of Lactate Metabolism Score in Breast and Thyroid Cancers to Assist Immunotherapy via Large-Scale Transcriptomic Data Analysis.

PubMed 2022/07/07(内容时间) Front Pharmacol Q1 · IF 5.4(JCR 2025)

研究概要

乳腺癌(BC)和甲状腺癌(TC)的发病率最高,尤其是在女性中。

中文摘要

乳腺癌(BC)和甲状腺癌(TC)发病率最高,尤其见于女性。既往研究发现,乳酸为癌细胞提供能量和合成代谢支持,是兼具细胞外与细胞内信号功能的重要致癌代谢物。但乳酸代谢评分与甲状腺癌和乳腺癌免疫特征的关系尚未系统分析。为研究乳酸在转录组层面的作用及其与BC和TC临床结局的相关性,研究者从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)收集1217例乳腺癌及568例甲状腺癌患者的转录组、临床和体细胞突变数据。根据单样本基因集富集分析(ssGSEA)计算乳酸代谢评分。结果显示,乳酸代谢相关基因及评分与乳腺癌和甲状腺癌患者生存显著相关。乳酸代谢评分还与HLA表达、TIL(肿瘤浸润淋巴细胞)浸润及干扰素(IFN)应答密切相关。此外,乳酸代谢评分是独立预后因素,可预测总生存、临床特征及免疫细胞浸润,有望用于BC和TC免疫治疗或精准化疗。

展开英文摘要原文

Breast cancer (BC) and thyroid cancer (TC) have the highest rate of incidence, especially in women. Previous studies have revealed that lactate provides energetic and anabolic support to cancer cells, thus serving as an important oncometabolite with both extracellular and intracellular signaling functions. However, the correlation of lactate metabolism scores with thyroid and breast cancer immune characteristics remains to be systematically analyzed. To investigate the role of lactate at the transcriptome level and its correlation with the clinical outcome of BC and TC, transcriptome data of 1,217 patients with breast cancer (BC) and 568 patients with thyroid cancer (TC) were collected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets with their corresponding clinical and somatic mutation data. The lactate metabolism score was calculated based on a single-sample gene set enrichment analysis (ssGSEA). The results showed that lactate metabolism-related genes and lactate metabolism scores was significantly associated with the survival of patients with BRCA and THCA. Notably, the lactate metabolism scores were strongly correlated with human leukocyte antigen (HLA) expression, tumor-infiltrating lymphocyte (TIL) infiltration, and interferon (IFN) response in BC and TC. Furthermore, the lactate metabolism score was an independent prognostic factor and could serve as a reliable predictor of overall survival, clinical characteristics, and immune cell infiltration, with the potential to be applied in immunotherapy or precise chemotherapy of BC and TC.

论文信息

作者
Wang C、Qu Z、Chen L、Pan Y、Tang Y、Hu G、Gao R、Niu R
第一作者单位
Department of Breast Surgery, Huangpu Branch, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.China
通讯作者单位
Department of Breast Surgical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.China
期刊
Frontiers in pharmacology2022
原文标识
PubMed 35873566 · DOI 10.3389/fphar.2022.928419