Wang Cheng, Qu Zheng, Chen Li, Pan Yunhao, Tang Yiqing, Hu Guangfu, Gao Ran, Niu Ruijie, Liu Qiang, Gao Xingyan, Fang Yi
Department of Breast Surgery, Huangpu Branch, Shanghai Ninth People's Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
Front Pharmacol. 2022 Jul 7;13:928419. doi: 10.3389/fphar.2022.928419. eCollection 2022.
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 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.
乳腺癌（BC）和甲状腺癌（TC）的发病率最高，尤其是在女性中。先前的研究表明，乳酸为癌细胞提供能量和合成代谢支持，因此作为一种重要的肿瘤代谢物，具有细胞外和细胞内信号传导功能。然而，乳酸代谢评分与甲状腺癌和乳腺癌免疫特征之间的相关性仍有待系统分析。为了研究乳酸在转录组水平上的作用及其与乳腺癌和甲状腺癌临床结局的相关性，我们从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中收集了1217例乳腺癌患者和568例甲状腺癌患者的转录组数据，以及相应的临床和体细胞突变数据。基于单样本基因集富集分析（ssGSEA）计算乳酸代谢评分。结果表明，乳酸代谢相关基因和乳酸代谢评分与BRCA和THCA患者的生存率显著相关。值得注意的是，乳酸代谢评分与乳腺癌和甲状腺癌中的人类白细胞抗原（HLA）表达、肿瘤浸润淋巴细胞（TIL）浸润和干扰素（IFN）反应密切相关。此外，乳酸代谢评分是一个独立的预后因素，可以作为总生存、临床特征和免疫细胞浸润的可靠预测指标，有可能应用于乳腺癌和甲状腺癌的免疫治疗或精准化疗。
