Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009 Zhejiang, China.
Orthopedics Research Institute of Zhejiang University, Hangzhou, 310009 Zhejiang, China.
Biomed Res Int. 2022 Jun 25;2022:4123622. doi: 10.1155/2022/4123622. eCollection 2022.
This study is aimed at identifying the important biomarkers associated with bone metastasis (BM) in breast cancer (BRCA).
The GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and DEG-related pathways were then explored. Further, we constructed the protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes. We then performed the Cox regression, Kaplan-Meier analysis, nomogram, and ROC curve to filter the most significant prognosis genes. The GSE14020 and GSE124647 datasets were used to verify the expression and prognostic value of hub genes, respectively. Finally, the gene set enrichment analysis (GSEA) was performed to reveal the potential mechanism.
Totally, 74 DEGs were detected, which mainly correlated with infectious disease, signaling molecules, and interaction. The 5 important DEGs were then filtered, and the Cox regression further showed that 2 genes, including prominin 1 (PROM1) and C-C motif chemokine ligand 2 (CCL2), were related to the prognosis of BRCA metastasis patients. Especially, PROM1 presented a better prognostic performance on the survival probability of patients than CCL2. Verification analysis further confirmed the abnormal expression and significant prognostic influence of PROM1. Finally, GSEA revealed that PROM1 was negatively related to IGF1 and mTOR pathways in BRCA metastasis.
PROM1 was an important biomarker associated with BRCA bone metastasis and affected the prognosis of metastatic BRCA patients. It may play a vital role in metastatic BRCA by negatively regulating IGF1 and mTOR pathways.
本研究旨在确定与乳腺癌(BRCA)骨转移(BM)相关的重要生物标志物。
使用 GSE175692 数据集检测 BRCA 样本中有无 BM 的差异表达基因(DEGs),并探索 DEG 相关途径。进一步,我们构建了 GEGs 的蛋白质-蛋白质相互作用(PPI)网络,并筛选了 5 个重要节点。然后,我们进行了 Cox 回归、Kaplan-Meier 分析、列线图和 ROC 曲线,以筛选最显著的预后基因。使用 GSE14020 和 GSE124647 数据集分别验证了枢纽基因的表达和预后价值。最后,进行了基因集富集分析(GSEA)以揭示潜在的机制。
总共检测到 74 个 DEGs,主要与传染病、信号分子和相互作用有关。然后筛选出 5 个重要的 DEGs,Cox 回归进一步表明,包括 prominin 1(PROM1)和 C-C 基序趋化因子配体 2(CCL2)在内的 2 个基因与 BRCA 转移患者的预后有关。特别是,PROM1 对患者的生存概率的预后性能优于 CCL2。验证分析进一步证实了 PROM1 的异常表达和对 BRCA 转移患者的显著预后影响。最后,GSEA 显示 PROM1 在 BRCA 转移中与 IGF1 和 mTOR 途径呈负相关。
PROM1 是与 BRCA 骨转移相关的重要生物标志物,影响转移性 BRCA 患者的预后。它可能通过负向调节 IGF1 和 mTOR 途径在转移性 BRCA 中发挥重要作用。