Transcriptome-Based Network Analysis Unveils Eight Immune-Related Genes as Molecular Signatures in the Immunomodulatory Subtype of Triple-Negative Breast Cancer

Frontiers in Oncology

Guoxiong Xu¹  Xiaolin Xu²  Jinguo Zhang²  Xin Li²  Li Wang³  Wencai Guan⁴  Ting Meng⁴ 

[1] Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai, China;Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China;Department of Pathology, Jinshan Hospital, Fudan University, Shanghai, China;Research Center for Clinical Medicine, Jinshan Hospital, Fudan University, Shanghai, China;

关键词: breast cancer;    gene signature;    immunomodulatory subtype;    overall survival;    transcriptome-based network;    WGCNA;   

DOI  :  10.3389/fonc.2020.01787

来源: DOAJ

【 摘 要 】

Objective: Triple-negative breast cancer (TNBC) is a high heterogeneity cancer. The identification of genomic aberrations that drive each of the TNBC subtypes may predict the prognosis of patients with TNBC and provide novel therapeutic strategies in clinical practice. This study focuses on the transcriptome-based gene expression of TNBC and aims to generate comprehensive gene co-expression networks correlated with the immune-related subtype of TNBC.Methods: The transcriptome profiles of 107 female patients with TNBC were analyzed. Weighted gene co-expression network analysis (WGCNA) was applied to construct related networks and to sort hub-genes associated with the survival of TNBC patients. The data of the transcriptional expression, genomic alteration, survival status, and tumor immune microenvironment, which associated with hub-genes, were extracted, retrieved, and analyzed from Oncomine, UALCAN, TCGA, starBase, Kaplan–Meier Plotter, cBioPortal, and TIMER databases.Results: Immune-related hub-genes, including BIRC3, BTN3A1, CSF2RB, GIMAP7, GZMB, HCLS1, LCP2, and SELL, were found to be associated with clinical features of TNBC evaluated by WGCNA. These hub-genes belonged to the immunomodulatory subtype of TNBC and were upregulated in the TNBC cells. The protein expression of eight immune-related hub-genes was further confirmed to be upregulated in TNBC/CD8+ tissues detected by immunohistochemical staining. Survival analysis revealed that overexpression of eight immune-related hub-genes was in favor of the survival of patients with TNBC. Moreover, a positive correlation between eight immune-related hub-genes and immune cell infiltration was observed in TNBC patients. Furthermore, checkpoint inhibitor genes such as PD-L1, PD-1, and CTLA4 were more enrichment in the immunomodulatory subtype of TNBC and the expression of PD-L1, PD-1, and CTLA4 was positively correlated with eight immune-related hub-genes in the breast cancer dataset of TCGA.Conclusions: Eight immune-related hub-genes were identified to be molecular signatures in the immunomodulatory subtype of TNBC, which may provide therapeutic targets for the treatment of patients with breast cancer.

【 授权许可】

Unknown