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

Author:

Cao Yukun1,Cao Jing1,Zou Peng2,Wang Shouman1

Affiliation:

1. Central South University

2. First Affiliated Hospital of Heilongjiang University of Chinese Medicine, Heilongjiang University of Chinese Medicine

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.

Publisher

Research Square Platform LLC

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