基于多灶性胶质母细胞瘤整合基因组分析脑胶质瘤复发相关生物标志物的研究
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国家自然科学基金项目(81972337);北京市自然科学基金杰出青年科学基金项目(JQ20030)


Identification of biomarkers study related to glioma recurrence based on integrated genomic analysis of multifocal glioblastoma
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    目的 基于多灶性胶质母细胞瘤(M-GBM)基因组分析脑胶质瘤复发相关生物标志物,为 了解潜在的发病机制和制订针对性的治疗策略提供依据。方法 选择中国脑胶质瘤基因组图谱(CGGA) 中 1 例胶质母细胞瘤患者的原发性和非同步性肿瘤样本的基因组进行高通量测序,并通过单核苷酸变 异(SNV)和基因组重排进行验证。对差异基因进行筛选,并将所测序数据的差异基因纳入 CGGA_325 和 CGGA_693 两个数据库中进行 Kaplan-Meier 生存曲线分析。结果 在原发性和非同步性肿瘤中分别 检测到 14 322、16 464 个 SNV,其中 4 744 个(33.1%)SNV 是共有的。1 组基因重排存在于原发性和非同 步性肿瘤中,3 组基因重排存在于原发性肿瘤中但不存在于非同步性肿瘤中,1 组重排存在于非同步性 肿瘤中但不存在于原发性肿瘤中。生存曲线分析结果显示,总生存期和无进展生存期的差异有统计学 意义(P< 0.01),低风险组患者的生存优于高风险组。结论 祖先克隆的子代细胞可能较早发生分化, 然后平行进化产生M-GBM,尽管在重排全景图上存在总体差异,但两个病变有共同的祖先。一组生物 标志物可能与M-GBM 的复发和级别进展相关。临床可根据靶向治疗策略独立分析 M-GBM 患者不同位 置的病变,指导精准治疗。

    Abstract:

    Objective Biomarkers related to glioma recurrence were analyzed based on the genome of multifocal glioblastoma (M-GBM) to provide a basis for understanding the potential pathogenesis and formulating targeted treatment strategies. Methods The genome of a primary and asynchronous tumor sample from a glioblastoma patient in the Chinese Glioma Genome Map (CGGA) was selected for high-throughput sequencing, and verified by single nucleotide variation (SNV) and genome rearrangement. The differential genes are screened, and the differential genes of the sequenced data are included in CGGA_ 325 and CGGA_ 693 Kaplan Meier survival curve analysis was conducted in two databases. Results 14 322 and 16 464 SNVs were detected in primary and asynchronous tumors, respectively, of which 4 744 (33.1%) were common. One group of gene rearrangements exists in primary and asynchronous tumors, three groups of gene rearrangements exist in primary tumors but not in asynchronous tumors, and one group of gene rearrangements exists in asynchronous tumors but not in primary tumors. The results of survival curve analysis showed that the difference between total survival and progression free survival was statistically significant (P < 0.01). The survival of low-risk group was better than that of high-risk group. Conclusions The progeny cells cloned by ancestors may differentiate earlier and then evolve in parallel to produce M-GBM, that is, although there are overall differences in the rearrangement panorama, the two lesions have a common ancestor. A set of biomarkers that may be related to the recurrence and grade progression of glioma. The clinic can independently analyze the lesions at different positions of M-GBM patients according to the targeted treatment strategy to guide the precise treatment.

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保肇实,王嘉义,李守巍,游赣.基于多灶性胶质母细胞瘤整合基因组分析脑胶质瘤复发相关生物标志物的研究[J].神经疾病与精神卫生,2022,22(12).
DOI :10.3969/j. issn.1009-6574.2022.12.005.

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  • 在线发布日期: 2023-02-17