INTRODUCTION Mitochondrial DNA(mtDNA) content in several solid tumors was found to be lower than in their normal counterparts. However, there is paucity of literature on the clinical significance of mtDNA content in glioblastoma and its effect on treatment response. Hence, we studied the prognostic significance of mtDNA content in glioblastoma tumor tissue and the effect of mtDNA depletion in glioblastoma cells on response to treatment MATERIALS AND METHODS: 130 newly diagnosed glioblastomas, 32 paired newly diagnosed and recurrent glioblastomas and 35 non-neoplastic brain tissues were utilized for the study. mtDNA content in the patient tumor tissue was assessed and compared with known biomarkers and patient survival. mtDNA was chemically depleted in malignant glioma cell lines, U87, LN229. The biology and treatment response of parent and depleted cells were compared RESULTS: Lower range of mtDNA copy number in glioblastoma was associated with poor overall survival(p=0.01), progression free survival(p=0.04) and also with wild type IDH (p=0.02). In recurrent glioblastoma, mtDNA copy number was higher than newly diagnosed glioblastoma in the patients who received RT (p=0.01). mtDNA depleted U87 and LN229 cells showed higher survival fraction post radiation exposure when compared to parent lines. The IC50 of TMZ was also higher for mtDNA depleted U87 and LN229 cells. The depleted cells formed more neurospheres than their parent counterparts, thus showing increased stemness of mtDNA depleted cells CONCLUSION: Low mtDNA copy number in glioblastoma is associated with poor patient survival and treatment resistance in cell lines possibly by impacting stemness of the glioblastoma cells.

中文翻译：

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低线粒体 DNA 拷贝数与胶质母细胞瘤的不良预后和治疗抵抗相关

介绍 发现几种实体瘤中的线粒体 DNA (mtDNA) 含量低于正常肿瘤。然而，关于胶质母细胞瘤中 mtDNA 含量的临床意义及其对治疗反应的影响的文献很少。因此，我们研究了胶质母细胞瘤肿瘤组织中 mtDNA 含量的预后意义以及胶质母细胞瘤细胞中 mtDNA 耗竭对治疗反应的影响 材料和方法：130 例新诊断的胶质母细胞瘤、32 对新诊断和复发的胶质母细胞瘤和 35 例非肿瘤性脑组织被用于研究。评估患者肿瘤组织中的 mtDNA 含量，并将其与已知的生物标志物和患者存活率进行比较。mtDNA 在恶性胶质瘤细胞系、U87、LN229 中被化学清除。比较亲代细胞和耗竭细胞的生物学和治疗反应结果：胶质母细胞瘤中较低范围的 mtDNA 拷贝数与较差的总生存期（p=0.01）、无进展生存期（p=0.04）以及野生型 IDH（p =0.02）。在复发性胶质母细胞瘤中，接受放疗的患者的 mtDNA 拷贝数高于新诊断的胶质母细胞瘤（p=0.01）。与亲本细胞系相比，mtDNA 耗尽的 U87 和 LN229 细胞在辐射暴露后显示出更高的存活率。对于耗尽 mtDNA 的 U87 和 LN229 细胞，TMZ 的 IC50 也更高。耗竭的细胞比其亲本对应物形成更多的神经球，因此显示出 mtDNA 耗竭细胞的干性增加 结论：