Screening of immunosuppressive factors for biomarkers of breast cancer malignancy phenotypes and subtype-specific targeted therapy

• Published in: PeerJ (San Francisco, CA) Vol. 7; p. e7197
• Main Authors: Wang, Ping, Liu, Jiaxuan, Song, Yunlei, Liu, Qiang, Wang, Chao, Qian, Caiyun, Zhang, Shuhua, Zhu, Weifeng, Yang, Xiaohong, Wan, Fusheng, Liu, Zhuoqi, Luo, Daya
• Format: Journal Article
• Language: English
• Published: United States PeerJ. Ltd 27.06.2019; PeerJ, Inc; PeerJ Inc
• Subjects: Analysis; Angiogenesis; Biochemistry; Bioinformatics; Biological markers; Biomarker; Biomarkers; Breast cancer; Breast tumors; Cancer immunotherapy; Cancer screening; Cancer therapies; Cell adhesion & migration; DNA microarrays; Gene expression; Genes; Genetic aspects; Genomes; Immunohistochemistry; Immunology; Immunosuppressive factor; Interleukin 8; Laboratories; Malignancy; Medical prognosis; Medical research; Messenger RNA; Metastasis; mRNA; Oncology; Online databases; Online information services; Ontology; Pathology; PD-L1 protein; Phenotypes; Principal components analysis; RNA; Therapeutic applications; Therapeutic target; Transforming growth factor-b1; Transforming growth factors; Tumor cell lines; Tumors; Vascular endothelial growth factor; Western blotting; China; Immunosuppressive factor; Biomarker; Breast cancer; Online databases; Therapeutic target
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.7197

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.