Vasculogenic Mimicry Related Long Noncoding RNA Signature Reveals New Therapy Strategy in Breast Cancer

Abstract

Abstract Background Vasculogenic mimicry (VM) is linked closely to the tumorigenesis. However, VM-related lncRNAs (VRLs) involved in the mediation of breast cancer (BC) are still unknown. This research aimed to identify a prognostic signature of VRLs in BC and excavate its potential biological function. Methods We obtained RNA-seq and relevant clinical data from The Cancer Genome Atlas database. Then, Cox and the LASSO regression were utilized to construct a multigene signature. The Kaplan-Meier and ROC curves were plotted to evaluate the efficacy of the model. GO and KEGG pathway were performed for patients in high-risk and low-risk groups. SsGSEA and CIBERSORT algorithm were used to observe the relationship in high-risk and low-risk groups and immune cells. Furthermore, we analysed the inhibitory concentration (IC50) values of three representative anti-vasculogenesis drugs of BC in high-risk and low-risk groups to verify drug sensitivity. Results A VRL-based prognostic signature composed by SEMA3B-AS1, MAPT-AS1, AL355512.1 and AP005717.2 was constructed. According to the risk score calculated by this signature, BC patients were divided into high-risk and low-risk groups. Patients in the high-risk group inclined to have a worse prognosis. SsGSEA and CIBERSORT showed that the majority of immune cells e.g., macrophage and CD4 T cell expressed notably higher in high-risk group (p < 0.05). In addition, we analysed the IC50 values of sorafenib, axitinib and AZD4547 in high-risk and low-risk groups, and all these drugs demonstrated favorable sensitivity to high-risk group which indicated that patients in high-risk group might benefit from anti-vasculogenesis drugs. Conclusions Based on bioinformatic analysis, we established a VM-related gene signature to predict the overall survival of BC patients. Apart from this, we characterized the relationship in the signature, immune microenvironment and correlated drugs which may ignite a novel idea of BC therapy.