3 级星形细胞瘤和少突胶质细胞瘤的瘤内分子异质性及其对疾病预后的意义

P. V. Nikitin, A. Belyaev, G. R. Musina, G. Kobyakov, I. N. Pronin, D. Usachev
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摘要

简介恶性脑肿瘤,如无性星形细胞瘤和无性少突胶质细胞瘤 3 级,具有高度侵袭性,是严重的临床问题。本研究主要评估无弹性星形细胞瘤和无弹性少突胶质细胞瘤的瘤内异质性及其对疾病预后的影响。研究瘤内异质性的特征,尤其是Ⅲ级星形细胞瘤和少突胶质细胞瘤组的坏死、血管增生、有丝分裂和对胶质瘤进展最重要的基因突变等形态学标准,以及这些参数对预后的意义分析。研究包括 389 例 IDH 突变星形细胞瘤患者和 200 例少突胶质细胞瘤患者。星形细胞瘤的平均Ki-67标记指数为12.78%,少突胶质细胞瘤为8.54%。出现血管增生、坏死、肉瘤样区占标本面积的 20% 以上以及有丝分裂的数量不仅会严重影响患者的无病存活率,还会影响其总存活率。在临床环境中,TERT启动子基因突变、表皮生长因子受体(EGFR)基因扩增和突变、CDKN2A基因缺失和TP53基因对无复发生存率和总生存率有明显的负面影响。单细胞 RNA 测序结果显示,包括肉瘤样区、TERT、表皮生长因子受体、CDKN2A 和 TP53 基因突变在内的其他因素也会导致所研究肿瘤的进展,并确保其恶性潜能的增加。
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Intra-tumoral molecular heterogeneity of grade 3 astrocytomas and oligodendrogliomas and its significance in disease prognosis
Introduction. Malignant brain tumors, such as anaplastic astrocytomas and anaplastic oligodendrogliomas grade 3, are characterized by high aggressiveness and pose a serious clinical problem. This study focuses on assessing intratumoral heterogeneity in anaplastic astrocytomas and anaplastic oligodendrogliomas and its impact on disease prognosis.Aim. To study characteristics of intratumoral heterogeneity, in particular such morphological criteria as necrosis, vascular proliferation, mitoses, and mutations in the most significant for glioma progression genes in the groups of grade III astrocytomas and oligodendrogliomas, as well as analysis of prognostic significance of these parameters.Materials and methods. The study included 389 patients with IDH-mutant astrocytomas and 200 patients with oligodendrogliomas. The mean Ki-67 labeling index of astrocytomas was 12.78 %, while that of oligodendrogliomas was 8.54 %.Results. The presence of vascular proliferation, necrosis, of more than 20 % of the area of the specimen occupied by sarcomatous-like areas and the number of mitoses significantly affected not only disease-free survival but also overall survival of patients. In the clinical setting, mutations in the TERT promoter gene, amplification and mutation of the EGFR gene, deletion of the CDKN2A gene, and TP53 gene had a significant negative impact on recurrence-free and overall survival.Conclusion. The results of single-cell RNA sequencing showed additional factors, including sarcomatous-like areas, as well as TERT, EGFR, CDKN2A and TP53 mutations, in the progression of the tumors under consideration and in ensuring an increase in their malignant potential.
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