下一代肿瘤不可知靶点即将出现
Next-generation tumor-agnostic targets on the horizon.
肿瘤不可知药物开发将肿瘤学重新聚焦于共享的分子依赖性而非组织来源,从而能够针对跨肿瘤的罕见可操作驱动因素进行高效开发。
英文原题:RAMP1 as a novel prognostic biomarker in pan-cancer and osteosarcoma.
高RAMP1表达相对于低RAMP1表达与不良预后相关(p < 0.05)。
受体活性修饰蛋白1(RAMP1)促进降钙素样受体(CLR)定位至质膜,但其在骨肉瘤(OS)中的作用仍不清楚。我们评估了RAMP1在不同癌症中的表达及预后价值,并研究了肿瘤免疫浸润。使用GSE39058和TARGET数据集分析预后价值。评估了差异基因表达。构建了蛋白-蛋白相互作用网络,并进行了基因集富集分析。分析了RAMP1在肿瘤微环境中的功能,并使用定量实时PCR验证了其在OS细胞系中的表达。相对于低RAMP1表达,高RAMP1表达与不良预后相关(p < 0.05)。低RAMP1表达与CD4+记忆活化T细胞丰度相关,而高表达水平与γδ T细胞高比例相关。来自TARGET的差异表达基因富集于嗅觉转导通路(归一化富集分数[NES] = 1.6998,p < 0.0001)。RAMP1表达与CD44表达负相关,但与TNFSF9表达正相关。与正常成骨细胞系hFOB1.19相比,RAMP1基因在OS细胞中大量表达。因此,RAMP1可能是OS的预后生物标志物和潜在治疗靶点。
Receptor activity modifying protein 1 (RAMP1) facilitates the localization of the calcitonin-like receptor (CLR) to the plasma membrane, but its role in osteosarcoma (OS) remains unclear. We evaluated the RAMP1 expression and prognostic value across different cancers, studying tumor immune infiltration. The prognostic value was analyzed using the GSE39058 and TARGET datasets. Differential gene expression was evaluated. a protein-protein interaction network was constructed, and gene set enrichment analysis was performed. The function of RAMP1 in the tumor microenvironment was analyzed, and its expression in OS cell lines was validated using quantitative real-time PCR. High RAMP1 expression correlated with poor prognosis relative to low RAMP1 expression (p < 0.05). Low RAMP1 expression correlated with an abundance of CD4+ memory-activated T cells. whereas a high expression level correlated with a high proportion of gamma-delta T cells (γδ T cells). Differentially expressed genes from TARGET was enriched in olfactory transduction pathways (normalized enrichment scores [NES] = 1.6998, p < 0.0001). RAMP1 expression negatively correlated with CD44 expression but positively correlated with TNFSF9 expression. The RAMP1 gene is substantially expressed in OS cells compared to the normal osteoblast cell line hFOB1.19. Thus, RAMP1 may be a prognostic biomarker and potential therapeutic target in OS.
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