Zheng Weicheng, Zhang Ruolan, Huang Ziru, Li Jianpeng, Wu Haonan, Zhou Yuwei, Zhu Jinwei, Wang Xianlong
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Department of Bioinformatics, School of Medical Technology and Engineering, Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
Front Mol Biosci. 2022 Apr 14;9:806727. doi: 10.3389/fmolb.2022.806727. eCollection 2022.
Telomerase reverse transcriptase promoter (-p) mutation has been frequently found, but associated with contrary prognosis, in both low-grade gliomas and glioblastomas. For the low-grade gliomas (Grades II-III), -p mutant patients have a better prognosis than the wildtype patients, whereas for the GBMs (Grade IV), -p mutation is related to a poor prognosis. We hypothesize that there exist high-risk patients in LGGs who share GBM-like molecular features, including -p mutation, and need more intensive treatment than other LGGs. A molecular signature is needed to identify these high-risk patients for an accurate and timely treatment. Using the within-sample relative expression orderings of gene pairs, we identified the gene pairs with significantly stable REOs, respectively, in both the -p mutant LGGs and GBMs but with opposite directions in the two groups. These reversely stable gene pairs were used as the molecular signature to stratify the LGGs into high-risk and low-risk groups. A signature consisting of 21 gene pairs was developed, which can classify LGGs into two groups with significantly different overall survival. The high-risk group has a similar genetic mutation profile and a similar survival profile as GBMs, and these high-risk tumors may progress to a more malignant state. The 21 gene-pair signature based on REOs is capable of identifying high-risk patients in LGGs and guiding the clinical choice for appropriate and timely intervention.
端粒酶逆转录酶启动子（-p）突变在低级别胶质瘤和胶质母细胞瘤中均频繁被发现，但与相反的预后相关。对于低级别胶质瘤（II-III级），-p突变患者的预后优于野生型患者，而对于胶质母细胞瘤（IV级），-p突变与预后不良相关。我们假设在低级别胶质瘤中存在具有类似胶质母细胞瘤分子特征（包括-p突变）的高危患者，他们需要比其他低级别胶质瘤患者更强化的治疗。需要一种分子特征来识别这些高危患者，以便进行准确及时的治疗。利用基因对的样本内相对表达排序，我们分别在-p突变的低级别胶质瘤和胶质母细胞瘤中鉴定出具有显著稳定的相对表达排序（REOs）的基因对，但两组中的方向相反。这些反向稳定的基因对被用作分子特征，将低级别胶质瘤分为高危和低危组。开发了一个由21个基因对组成的特征，它可以将低级别胶质瘤分为两组，其总生存期有显著差异。高危组具有与胶质母细胞瘤相似的基因突变谱和生存谱，这些高危肿瘤可能进展为更恶性的状态。基于相对表达排序的21个基因对特征能够识别低级别胶质瘤中的高危患者，并指导临床选择合适及时的干预措施。
