Research Paper Volume 16, Issue 9 pp 8086—8109
Constructing a novel prognostic model for triple-negative breast cancer based on genes associated with vasculogenic mimicry
- 1 Department of Clinical Medicine, Guizhou Medical University, Guiyang, China
- 2 Department of Breast Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China
- 3 Information Department of Guizhou Provincial People’s Hospital, Guiyang, China
- 4 Department of Breast Surgery, Guiyang Maternal and Child Health Care Hospital, Guiyang, China
- 5 The Maternal and Child Health Care Hospital of Guizhou Medical University, Guiyang, China
Received: October 13, 2023 Accepted: March 18, 2024 Published: May 8, 2024
https://doi.org/10.18632/aging.205806How to Cite
Copyright: © 2024 Ren et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Research has shown a connection between vasculogenic mimicry (VM) and cancer progression. However, the functions of genes related to VM in the emergence and progression of TNBC have not been completely elucidated.
Methods: A survival risk model was constructed by screening biomarkers using DESeq2 and WGCNA based on public TNBC transcriptome data. Furthermore, gene set enrichment analysis was performed, and tumor microenvironment and drug sensitivity were analyzed. The selected biomarkers were validated via quantitative PCR detection, immunohistochemical staining, and protein detection in breast cancer cell lines. Biomarkers related to the proliferation and migration of TNBC cells were validated via in vitro experiments.
Results: The findings revealed that 235 target genes were connected to the complement and coagulation cascade pathways. The risk score was constructed using KCND2, NRP1, and VSTM4. The prognosis model using the risk score and pathological T stage yielded good validation results. The clinical risk of TNBC was associated with the angiogenesis signaling pathway, and the low-risk group exhibited better sensitivity to immunotherapy. Quantitative PCR and immunohistochemistry indicated that the expression levels of KCND2 in TNBC tissues were higher than those in adjacent nontumor tissues. In the TNBC cell line, the protein expression of KCND2 was increased. Knockdown of KCND2 and VSTM4 inhibited the proliferation and migration of TNBC cells in vitro.
Conclusions: In this study, three VM-related biomarkers were identified, including KCND2, NRP1, and VSTM4. These findings are likely to aid in deepening our understanding of the regulatory mechanism of VM in TNBC.