Wang Jun-Han, Xia Ji, Wu Peng-Fei, Yi Liang, Yu Shi-Cang
Department of Stem Cell and Regenerative Medicine, Southwest Hospital, Army Medical University, Chongqing, China.
International Joint Research Center for Precision Biotherapy, Southwest Hospital, Army Medical University, Chongqing, China.
Sci Rep. 2025 Sep 26;15(1):33194. doi: 10.1038/s41598-025-17539-4.
Glioblastoma (GBM) displays marked intratumoral heterogeneity and high invasiveness, making en bloc resection difficult. In particular, total/subtotal resection is challenging for lesions near the diencephalon, midbrain, or brainstem or in motor areas, as damage to these sites can compromise postoperative function and reduce quality of life. Resection of GBM, especially deep-seated tumors, rarely achieves circumferential margins; pathological examination can only be performed on a portion of the tumor. Notably, traditional random intraoperative sampling introduces bias, limiting molecular profiling. The use of imaging-based biomarkers may mitigate this sampling bias, but critical molecular-region signatures remain undefined. In this study, we identified imaging parameters on structural magnetic resonance perfusion imaging to facilitate targeted sampling of representative glioma regions. Whole-exome sequencing of 29 samples from 6 patients revealed significant intratumoral heterogeneity in gene mutations across sampling sites, with edge regions showing the highest heterogeneity. Key cancer driver and drug-target gene mutations also exhibited heterogeneous spatial distributions. Critically, regions with elevated perfusion-weighted imaging cerebral blood volume (PWI-CBV) values demonstrated greater mutation heterogeneity and enrichment of key mutation events. To ensure comprehensive detection of heterogeneous mutations intraoperatively, we propose a three-site sampling strategy within high PWI-CBV regions. This approach may increase the accuracy and completeness of molecular pathological data, ultimately supporting personalized therapeutic planning.
胶质母细胞瘤（GBM）表现出显著的肿瘤内异质性和高侵袭性，使得整块切除变得困难。特别是，对于间脑、中脑或脑干附近或运动区域的病变，全切除/次全切除具有挑战性，因为这些部位的损伤会损害术后功能并降低生活质量。GBM的切除，尤其是深部肿瘤，很少能达到切缘；病理检查只能对肿瘤的一部分进行。值得注意的是，传统的随机术中采样会引入偏差，限制分子分析。基于成像的生物标志物的使用可能会减轻这种采样偏差，但关键的分子区域特征仍未明确。在本研究中，我们在结构磁共振灌注成像上确定了成像参数，以促进对代表性胶质瘤区域的靶向采样。对6例患者的29个样本进行全外显子测序，结果显示跨采样部位的基因突变存在显著的肿瘤内异质性，边缘区域的异质性最高。关键的癌症驱动基因和药物靶点基因突变也表现出异质的空间分布。至关重要的是，灌注加权成像脑血容量（PWI-CBV）值升高的区域显示出更大的突变异质性和关键突变事件的富集。为了确保术中全面检测异质突变，我们提出了在高PWI-CBV区域内的三点采样策略。这种方法可能会提高分子病理数据的准确性和完整性，最终支持个性化治疗方案的制定。
