Coelho Karina Munhoz de Paula Alves, Dalmolin Matheus, Pedack Francis Rossetti, Pickler José Guilherme, Barbosa Camila, Recalde Julio, Blasius Rodrigo, Silva Bruna Louise, Fernandes Marcelo A C, Fronza Junior Hercilio, de França Paulo Henrique Condeixa, Roesler Rafael
Department of Scientific Development and Innovation (DECIPE), Center for Anatomo-Pathological Diagnosis (CEDAP), Joinville, Brazil.
National Science and Technology Institute for Children's Cancer Biology and Pediatric Oncology-INCT BioOncoPed, Porto Alegre, Brazil.
Childs Nerv Syst. 2025 Sep 11;41(1):277. doi: 10.1007/s00381-025-06913-2.
Twist1 is a transcription factor that regulates embryonic development, stemness, and differentiation, and can also stimulate initiation of tumorigenesis in peripheral solid cancers. However, its role in central nervous system tumors, including medulloblastoma (MB), the main type of malignant brain cancer that afflicts children, remains poorly understood. Here, we examined expression of Twist1, and its potential significance in prognosis, in different histological variants and molecular subgroups of MB.
Gene expression data for TWIST1 and corresponding overall survival (OS) of patients was analyzed in 612 MB samples using a previously described dataset. A cross-sectional analysis of Twist1 protein content in 24 MB tumor samples from patients was carried out by immunohistochemistry.
TWIST1 transcript levels were higher in classic MB compared to desmoplastic tumors. Within samples with classic histology, higher TWIST1 expression was associated with a longer OS. Tumors in the SHH subgroup had lower TWIST1 expression compared to all other subgroups, and Group 4 showed lower expression than WNT tumors. In Group 4 MB, higher TWIST1 levels were associated with shorter OS, whereas patients with SHH tumors and higher TWIST1 levels showed longer OS. Twist1 protein was detectable in part of classic and LCA MB tumors belonging to the SHH, WNT, or Group 3/4 subgroups.
We found opposite patterns of association between TWST1 and patient survival in Group 4 and SHH MB subgroups. Our results highlight the importance of stratifying tumors by molecular subgroup and histological classification when exploring novel potential biomarkers and therapeutic targets in MB.
Twist1是一种转录因子，可调节胚胎发育、干性和分化，还能刺激外周实体癌的肿瘤发生起始。然而，其在中枢神经系统肿瘤中的作用，包括髓母细胞瘤（MB），这种困扰儿童的主要恶性脑癌类型，仍知之甚少。在此，我们研究了Twist1在MB不同组织学变体和分子亚组中的表达及其在预后中的潜在意义。
使用先前描述的数据集，分析了612个MB样本中TWIST1的基因表达数据以及患者相应的总生存期（OS）。通过免疫组织化学对24例患者的MB肿瘤样本中Twist1蛋白含量进行横断面分析。
与促结缔组织增生型肿瘤相比，经典型MB中的TWIST1转录水平更高。在具有经典组织学的样本中，较高的Twist1表达与较长的OS相关。与所有其他亚组相比，SHH亚组中的肿瘤TWIST1表达较低，4组的表达低于WNT肿瘤。在4组MB中，较高的Twist1水平与较短的OS相关，而SHH肿瘤且Twist1水平较高的患者OS较长。在属于SHH、WNT或3/4组亚组的部分经典型和LCA MB肿瘤中可检测到Twist1蛋白。
我们在4组和SHH MB亚组中发现Twist1与患者生存之间存在相反的关联模式。我们的结果强调了在探索MB新的潜在生物标志物和治疗靶点时，按分子亚组和组织学分类对肿瘤进行分层的重要性。
