Wang Ping, Liu Jiaxuan, Song Yunlei, Liu Qiang, Wang Chao, Qian Caiyun, Zhang Shuhua, Zhu Weifeng, Yang Xiaohong, Wan Fusheng, Liu Zhuoqi, Luo Daya
Queen Mary School, Nanchang University, Nanchang, China.
Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, China.
PeerJ. 2019 Jun 27;7:e7197. doi: 10.7717/peerj.7197. eCollection 2019.
We aimed to screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodeled, and differentially expressed genes were identified. Weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) and KEGG pathway enrichment analysis were performed to explore the immune-related events related to the basal-like breast cancer. The online resources, GOBO, Kaplan-Meier Plotter and UALCAN, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. Immunohistochemistry was used to evaluate and levels in breast tumors and normal breast tissues; qPCRs and western blots were used to validate the expression of clinical immuno-oncology (IO) therapeutic targets () and IL8 in cell lines. The results showed that various immune-related events contribute to basal-like breast cancer. First, β and had higher average expression levels in more malignant cell lines; second, and had higher average expression levels in more malignant breast cancer tissues, and the high expression levels were associated with poor survival rate. Third, IO targets and which were confirmed to be more suitable for the treatment of basal-like breast cancer. In view of the above, during the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors, , β, , and are up-regulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.
我们旨在筛选并验证管腔型和基底样型乳腺癌细胞系及与恶性表型相关的组织样本中的免疫抑制因子。下载并重塑了mRNA微阵列数据集GSE40057和GSE1561，鉴定了差异表达基因。进行加权基因共表达网络分析（WGCNA）、基因本体（GO）和KEGG通路富集分析，以探索与基底样型乳腺癌相关的免疫相关事件。利用在线资源GOBO、Kaplan-Meier Plotter和UALCAN筛选与乳腺癌恶性表型相关的免疫抑制因子。采用免疫组织化学法评估乳腺肿瘤和正常乳腺组织中的 和 水平；采用qPCR和western blot法验证临床免疫肿瘤学（IO）治疗靶点 （ ）和IL8在细胞系中的表达。结果表明，多种免疫相关事件促成了基底样型乳腺癌。首先，β和 在恶性程度更高的细胞系中平均表达水平更高；其次， 和 在恶性程度更高的乳腺癌组织中平均表达水平更高，且高表达水平与低生存率相关。第三，IO靶点 和 被证实更适合用于基底样型乳腺癌的治疗。鉴于上述情况，在乳腺癌的形成和发展过程中，免疫相关基因总是被激活，免疫抑制因子 、β、 和 上调。这些分子可作为乳腺癌预后的生物标志物。然而，由于个体免疫相关因子可发挥多种生物学作用，免疫抑制因子与乳腺癌恶性表型之间的机制关系及其作为药物靶点应用的可行性需要进一步研究。
