Center for Genome Engineering, Institute for Basic Science, 55, Expo-ro, Yuseong-gu, Daejeon, 34126, Republic of Korea.
Department of Orthopaedic Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
J Neurooncol. 2023 Oct;165(1):113-126. doi: 10.1007/s11060-023-04458-5. Epub 2023 Oct 21.
The immortality of cancer cells relies on maintaining the length of telomeres, which prevents cellular senescence and enables unlimited replication. However, little is currently known about telomerase activity and the alternative lengthening of telomeres (ALT) in vestibular schwannomas. In this study we aimed to elucidate the role that telomerase and ALTs play in vestibular schwannomas.
To address this gap, we conducted a study where we used the gene set variation analysis algorithm with bulk RNA-seq and single-cell RNA-seq to identify the characteristics of each group of patients with vestibular schwannomas, based on their telomere maintenance mechanism subtype.
Our findings suggest that patients with relatively high ALT-like groups have a better prognosis than those with relatively high telomerase groups. Specifically, we found that the high telomerase group had relatively higher antigen-presenting cell (APC) activity than the high ALT like group. At the single-cell level, microglia, neutrophils, and fibroblasts showed high telomerase activity and relatively high APC activity compared to other cell types. In addition, Schwann cells in the group with low ALT levels exhibited elevated immune activity at the single-cell level.
These results suggest that personalized drug therapy could be developed from the perspective of precision medicine for patients with relatively high telomerase activity and a high ALT-like group.
癌细胞的永生依赖于端粒长度的维持，这可以防止细胞衰老，并实现无限复制。然而，目前对于前庭神经鞘瘤中端粒酶活性和端粒的非经典延长（ALT）知之甚少。在这项研究中，我们旨在阐明端粒酶和 ALT 在前庭神经鞘瘤中的作用。
为了解决这一差距，我们使用了批量 RNA-seq 和单细胞 RNA-seq 的基因集变异分析算法，根据端粒维持机制亚型，对每组前庭神经鞘瘤患者的特征进行了研究。
我们的研究结果表明，相对高 ALT 样组的患者比相对高端粒酶组的患者预后更好。具体来说，我们发现高端粒酶组的抗原呈递细胞（APC）活性相对高于高 ALT 样组。在单细胞水平上，与其他细胞类型相比，小胶质细胞、中性粒细胞和成纤维细胞表现出较高的端粒酶活性和相对较高的 APC 活性。此外，低 ALT 水平组的施万细胞在单细胞水平上表现出较高的免疫活性。
这些结果表明，从相对高端粒酶活性和高 ALT 样组患者的精准医学角度出发，可能可以开发出个性化药物治疗方法。
