Screening of immunosuppressive factors for biomarkers of breast cancer malignancy phenotypes and subtype-specific targeted therapy
Screening of immunosuppressive factors for biomarkers of breast cancer malignancy phenotypes and subtype-specific targeted therapy
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乳腺癌恶性表型生物标志物免疫抑制因子筛选及亚型特异性靶向治疗
作者：
Ping Wang;Jiaxuan Liu;Yunlei Song;Qiang Liu;Chao Wang;Caiyun Qian;Shuhua Zhang;Weifeng Zhu;Xiaohong Yang;Fusheng Wan;Zhuoqi Liu;Daya Luo
我们的目的是筛选和验证与恶性表型相关的管腔样和基底样乳腺癌细胞系和组织样本中的免疫抑制因子。下载mRNA微阵列数据集GSE 40057和GSE 1561并进行重构，并鉴定差异表达的基因。采用加权基因共表达网络分析（WGCNA）、基因本体（GO）和KEGG途径富集分析，探讨基底细胞样乳腺癌的免疫相关事件。采用GOBO、Kaplan-Meier Plotter和UALCAN等网络资源筛选与乳腺癌恶性表型相关的免疫抑制因子。使用免疫组织化学评价乳腺肿瘤和正常乳腺组织中的VEGFA和MIF水平;使用qPCR和蛋白质印迹验证细胞系中临床免疫肿瘤学（IO）治疗靶点CD 274（PD-L1）和IL 8的表达。结果表明，各种免疫相关事件有助于基底样乳腺癌。首先，TGFβ1和IL 8在恶性程度较高的细胞系中平均表达水平较高;其次，MIF和VEGFA在恶性程度较高的乳腺癌组织中平均表达水平较高，且高表达水平与较差的生存率相关。第三，IO靶向CD 274和IL 8，这两种靶向被证实更适合于基底细胞样乳腺癌的治疗。综上所述，在乳腺癌的形成和发展过程中，免疫相关基因始终处于激活状态，免疫抑制因子IL 8、TGFβ1、MIF、VEGFA表达上调。这些分子可用作乳腺癌预后的生物标志物。然而，由于个体免疫相关因子可以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。
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 VEGFA and MIF 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 CD274 (PD-L1) and IL8 in cell lines. The results showed that various immune-related events contribute to basal-like breast cancer. First, TGFβ1 and IL8 had higher average expression levels in more malignant cell lines; second, MIF and VEGFA 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 CD274 and IL8 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, IL8, TGFβ1, MIF, and VEGFA 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.
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影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3
作者：
G. Z. Cheng;Sungman Park;Shaokun Shu;Lili He;W. Kong;Weizhou Zhang;Z. Yuan;Lu‐Hai Wang;J. Cheng
通讯作者：
G. Z. Cheng;Sungman Park;Shaokun Shu;Lili He;W. Kong;Weizhou Zhang;Z. Yuan;Lu‐Hai Wang;J. Cheng
影响因子：
5.1
作者：
Marrero, Jorge A;Pelletier, Shawn
通讯作者：
Pelletier, Shawn
影响因子：
12.3
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Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
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Zhang J
影响因子：
1.5
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Gilles, HoChong;Garbutt, Tonora;Landrum, Jasmine
通讯作者：
Landrum, Jasmine