关键词: biomarkers glioblastoma immune-oncology nCounter prognosis

来  源:   DOI:10.1177/17588359221127678   PDF(Pubmed)

Abstract:
UNASSIGNED: Glioblastoma (GBM), isocitrate dehydrogenase (IDH) wild-type (IDH wt), and grade 4 astrocytomas, IDH mutant (IDH mut), are the most common and aggressive primary malignant brain tumors in adults. A better understanding of the tumor immune microenvironment may provide new biomarkers and therapeutic opportunities.
UNASSIGNED: We aimed to evaluate the expression profile of 730 immuno-oncology-related genes in patients with IDH wt GBM and IDH mut tumors and identify prognostic biomarkers and a gene signature associated with patient survival.
UNASSIGNED: RNA was isolated from formalin-fixed, paraffin-embedded sections of 99 tumor specimens from patients treated with standard therapy. Gene expression profile was assessed using the Pan-Cancer Immune Profiling Panel (Nanostring Technologies, Inc., Seattle, WA, USA). Data analysis was performed using nSolverSoftware and validated in The Cancer Genome Atlas. In addition, we developed a prognostic signature using the cox regression algorithm (Least Absolute Shrinkage and Selection Operator).
UNASSIGNED: We found 88 upregulated genes, high immunological functions, and a high macrophage score in IDH wt GBM compared to IDH mut tumors. Regarding IDH wt GBM, we found 24 upregulated genes in short-term survivors (STS) and overexpression of CD274 (programmed death-ligand 1, PD-L1). Immune pathways, CD45, cytotoxic, and macrophage scores were upregulated in STS. Two different prognostic groups were found based on the 12-gene signature (CXCL14, PSEN2, TNFRSF13C, IL13RA1, MAP2K1, TNFSF14, THY1, CTSL, ITGAE, CHUK, CD207, and IFITM1).
UNASSIGNED: The elevated expression of immune-oncology-related genes was associated with worse outcome in IDH wt GBM patients. Increased immune functions, CD45, cytotoxic cells, and macrophage scores were associated with a more aggressive phenotype and may provide promising possibilities for therapy. Moreover, a 12 gene-based signature could predict patients\' prognosis.
摘要:
未经证实:胶质母细胞瘤(GBM),异柠檬酸脱氢酶(IDH)野生型(IDHwt),和4级星形细胞瘤,IDH突变体(IDHmut),是成人中最常见和侵袭性的原发性恶性脑肿瘤。更好地了解肿瘤免疫微环境可能提供新的生物标志物和治疗机会。
UNASSIGNED:我们旨在评估IDHwtGBM和IDHmut肿瘤患者中730个免疫肿瘤学相关基因的表达谱,并确定与患者生存相关的预后生物标志物和基因特征。
未经鉴定:从福尔马林固定的RNA中分离,来自接受标准治疗的患者的99个肿瘤标本的石蜡包埋切片。使用泛癌免疫分析小组(NanostringTechnologies,Inc.,西雅图,WA,美国)。使用nSolverSoftware进行数据分析,并在癌症基因组图谱中进行验证。此外,我们使用cox回归算法(最小绝对收缩和选择算子)开发了预后特征。
未经证实:我们发现了88个上调的基因,高免疫功能,与IDHmut肿瘤相比,IDHwtGBM的巨噬细胞得分较高。关于IDHwtGBM,我们在短期存活者(STS)和CD274(程序性死亡-配体1,PD-L1)过表达中发现了24个上调的基因.免疫途径,CD45,细胞毒性,STS中巨噬细胞评分上调。根据12个基因签名发现了两个不同的预后组(CXCL14,PSEN2,TNFRSF13C,IL13RA1,MAP2K1,TNFSF14,THY1,CTSL,ITGAE,CHUK,CD207和IFITM1)。
未经证实:肿瘤免疫相关基因的表达升高与IDHwtGBM患者的不良预后相关。增强免疫功能,CD45细胞毒性细胞,和巨噬细胞评分与更具侵袭性的表型相关,可能为治疗提供有希望的可能性.此外,基于12个基因的签名可以预测患者的预后。
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