Lin Shuai, Tan Zengqi, Cui Hanxiao, Ma Qilong, Zhao Xuyan, Wu Jianhua, Dai Luyao, Kang Huafeng, Guan Feng, Dai Zhijun
Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Joint International Research Laboratory of Glycobiology and Medicinal Chemistry, College of Life Sciences, Northwest University, Xi'an, China.
Front Oncol. 2022 Sep 14;12:854284. doi: 10.3389/fonc.2022.854284. eCollection 2022.
Breast cancer is one of the most important diseases in women around the world. Glycosylation modification correlates with carcinogenesis and roles of glycogenes in the clinical outcome and immune microenvironment of breast cancer are unclear.
A total of 1297 breast cancer and normal cases in the TCGA and GTEx databases were enrolled and the transcriptional and survival information were extracted to identify prognostic glycogenes using Univariate Cox, LASSO regression, Multivariate Cox analyses and Kaplan-Meier method. The immune infiltration pattern was explored by the single sample gene set enrichment method. The HLA and immune checkpoint genes expression were also compared in different risk groups. The expressions of a glycogene MGAT5 as well as its products were validated by immunohistochemistry and western blotting in breast cancer tissues and cells.
A 19-glycogene signature was identified to separate breast cancer patients into high- and low-risk groups with distinct overall survival rates ( < 0.001). Compared with the high-risk group, proportion of naive B cells, plasma cells and CD8 T cells increased in the low-risk group ( < 0.001). Besides, expressions of HLA and checkpoint genes, such as CD274, CTLA4, LAG3 and TIGIT3, were upregulated in low-risk group. Additionally, highly expressed MGAT5 was validated in breast cancer tissues and cells. Downstream glycosylation products of MGAT5 were all increased in breast cancer.
We identified a 19-glycogene signature for risk prediction of breast cancer patients. Patients in the low-risk group demonstrated a higher immune infiltration and better immunotherapy response. The validation of MGAT5 protein suggests a probable pathway and target for the development and treatment of breast cancer.
乳腺癌是全球女性最重要的疾病之一。糖基化修饰与致癌作用相关，而糖基因在乳腺癌临床结局和免疫微环境中的作用尚不清楚。
纳入TCGA和GTEx数据库中的1297例乳腺癌及正常病例，提取转录和生存信息，采用单因素Cox分析、LASSO回归、多因素Cox分析及Kaplan-Meier法鉴定预后糖基因。通过单样本基因集富集法探索免疫浸润模式。还比较了不同风险组中HLA和免疫检查点基因的表达。通过免疫组织化学和蛋白质印迹法在乳腺癌组织和细胞中验证了糖基因MGAT5及其产物的表达。
鉴定出一个由19个糖基因组成的特征，可将乳腺癌患者分为总生存率不同的高风险组和低风险组（<0.001）。与高风险组相比，低风险组中幼稚B细胞、浆细胞和CD8 T细胞的比例增加（<0.001）。此外，低风险组中HLA和检查点基因如CD274、CTLA4、LAG3和TIGIT3的表达上调。此外，在乳腺癌组织和细胞中验证了MGAT5的高表达。MGAT5的下游糖基化产物在乳腺癌中均增加。
我们鉴定出一个用于预测乳腺癌患者风险的19个糖基因组成的特征。低风险组患者表现出更高的免疫浸润和更好的免疫治疗反应。MGAT5蛋白的验证提示了乳腺癌发生发展及治疗的可能途径和靶点。
