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Pan-Cancer Analyses Reveal Prognostic Value of Osteomimicry Across 20 Solid Cancer Types

机译:泛癌分析揭示了骨质癌患者的预后价值

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Background: Osteomimicry of cancer cells had been widely reported in prostate cancer and breast cancer. However, the prognostic value of osteomimicry in various cancer types remained unclear. We hypothesized that osteomimicry would result in remodeling of the tumor microenvironment and was eligible to predict patient prognosis. Methods: A comprehensive transcriptomic analysis of the osteomimicry, which was characterized by mRNA expression of SPARC, SPP1 and BGLAP, across 20 solid tumors (7564 patients) using RNA-seq data from The Cancer Genome Atlas (TCGA) was conducted. Samples of each cancer type were classified into subgroups (high vs. low) based on median value of osteomimetic markers, the associations of these markers with clinical outcomes, immune cell infiltration and immune checkpoints expression were explored. Results: Each osteomimetic marker harbored prognostic value in the pan-cancer analyses (SPARC: hazard ratio (HR)=1.10, p=0.028; SPP1: HR=1.25, p0.001; BGLAP: HR=1.13, p=0.005). Patients with high expression of all the three genes also had significantly unfavorable survival (HR=1.61, p0.0001) compared with those of low expression. Correlation analyses demonstrated that osteomimicry was closely related to tumor purity, dendritic cells (DC) infiltration and expression of immune checkpoints. Conclusions: Osteomimicry had prognostic value in various cancer types and the underlying mechanism might correlate to the trapping and dysfunction of DCs in the tumor microenvironment, revealing the potential of osteomimicry as a target of immunotherapy.
机译:背景:前列腺癌和乳腺癌的癌细胞骨质瘤被广泛报道。然而,各种癌症类型中的骨瘤的预后值仍不清楚。我们假设骨质化会导致肿瘤微环境的重塑,并有资格预测患者预后。方法:对骨质瘤的综合转录组分析,其特征在于使用来自癌症基因组Atlas(TCGA)的RNA-SEQ数据的20种实体瘤(7564名患者)的SPARC,SPP1和BGLAP的mRNA表达。基于骨质染色标记物的中值,每种癌症类型的样品分为亚组(高与低),这些标志物与临床结果,免疫细胞浸润和免疫检查点表达的这些标志物的缔合。结果:每个骨瘤标志物在泛癌分析中覆有预后值(SPARC:危害比(HR)= 1.10,P = 0.028; SPP1:HR = 1.25,P <0.001; BGLAP:HR = 1.13,P = 0.005)。与低表达相比,患有所有三种基因的高表达的患者也具有显着不利的存活(HR = 1.61,P <0.0001)。相关性分析证明,骨质化与肿瘤纯度,树突细胞(DC)浸润和免疫检查点的表达密切相关。结论:骨质瘤在各种癌症类型中具有预后价值,并且潜在的机制可能与肿瘤微环境中DCS的诱捕和功能障碍相关,揭示骨质化的潜力作为免疫疗法的靶标。

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