Glioma stem cell signature predicts the prognosis and the response to tumor treating fields treatment.

Glioma stem cell signature predicts the prognosis and the response to tumor treating fields treatment.
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DOI:
10.1111/cns.13956
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发表时间:
2022-12
影响因子:
5.5
通讯作者:
--
中科院分区:
医学1区
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--
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胶质瘤干细胞(GSC)在胶质瘤复发和化疗-放疗(CRT)抵抗中起重要作用。目前,缺乏针对GSC的有效治疗方法。本研究旨在探索GSC富集胶质瘤患者的潜在个性化治疗。使用单细胞RNA测序(scRNA-seq)鉴定GSC相关基因。然后,应用机器学习方法进行聚类和验证。采用最小绝对收缩和选择算子(LASSO)和考克斯回归构建风险评分。进行生存分析。此外,在高风险和低风险评分组中评价了放化疗耐药的发生率、免疫治疗状态和肿瘤治疗野(TTF)治疗反应。两个GSC集群表现出显着不同的干指数,免疫微环境,和基因组改变。基于GSC聚类,构建了11基因GSC风险评分,其对预后具有较高的预测价值。在治疗方面,GSC风险评分高的患者对化疗耐药的风险更高。TTF治疗可以全面抑制高GSC风险评分胶质瘤的恶性生物学特性。我们的研究构建了由11个GSC特异性基因组成的GSC标签,并确定了其在胶质瘤中的预后价值。TTF是GSC富集胶质瘤患者的一种有前途的治疗方法。我们将胶质瘤患者分为高胶质瘤干细胞和低胶质瘤干细胞(GSC)组。与低GSC患者相比,GSC富集患者的化疗耐药性更高,预后更差。肿瘤治疗野(TTF)治疗可以有效抑制GSC富集胶质瘤的恶性生物学特性,包括有丝分裂、血管生成、迁移和侵袭潜力。TTF还可以打破GSC富集的胶质瘤中的原始DNA平衡。总之,TTF是一种有前途的GSC富集胶质瘤患者的治疗方法。
Glioma stem cells (GSCs) play an important role in glioma recurrence and chemo‐radiotherapy (CRT) resistance. Currently, there is a lack of efficient treatment approaches targeting GSCs. This study aimed to explore the potential personalized treatment of patients with GSC‐enriched gliomas. Single‐cell RNA sequencing (scRNA‐seq) was used to identify the GSC‐related genes. Then, machine learning methods were applied for clustering and validation. The least absolute shrinkage and selection operator (LASSO) and COX regression were used to construct the risk scores. Survival analysis was performed. Additionally, the incidence of chemo‐radiotherapy resistance, immunotherapy status, and tumor treating field (TTF) therapy response were evaluated in high‐ and low‐risk scores groups. Two GSC clusters exhibited significantly different stemness indices, immune microenvironments, and genomic alterations. Based on GSC clusters, 11‐gene GSC risk scores were constructed, which exhibited a high predictive value for prognosis. In terms of therapy, patients with high GSC risk scores had a higher risk of resistance to chemotherapy. TTF therapy can comprehensively inhibit the malignant biological characteristics of the high GSC‐risk‐score gliomas. Our study constructed a GSC signature consisting of 11 GSC‐specific genes and identified its prognostic value in gliomas. TTF is a promising therapeutic approach for patients with GSC‐enriched glioma. We divided glioma patients into the high‐ and low‐glioma stem cell (GSC) groups. GSC‐enriched patients had higher chemo‐radiotherapy resistance and worse prognosis than low‐GSC patients. Tumor treating field (TTF) therapy can effectively inhibit malignant biological characteristics of GSC‐enriched gliomas, including mitosis, angiogenesis, migration and invasion potential. TTF also could break the original DNA balance in GSC‐enriched gliomas. Taken together, TTF is a promising therapeutic approach for GSC‐enriched glioma patients.
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