The Machine-Learning-Mediated Interface of Microbiome and Genetic Risk Stratification in Neuroblastoma Reveals Molecular Pathways Related to Patient Survival.
The Machine-Learning-Mediated Interface of Microbiome and Genetic Risk Stratification in Neuroblastoma Reveals Molecular Pathways Related to Patient Survival.
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DOI：
10.3390/cancers14122874
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发表时间：
2022-06-10
期刊：
影响因子：
5.2
通讯作者：
Zhong, Jiang
中科院分区：
文献类型：
--
作者：
Li, Xin;Wang, Xiaoqi;Huang, Ruihao;Stucky, Andres;Chen, Xuelian;Sun, Lan;Wen, Qin;Zeng, Yunjing;Fletcher, Hansel;Wang, Charles;Xu, Yi;Cao, Huynh;Sun, Fengzhu;Li, Shengwen Calvin;Zhang, Xi;Zhong, Jiang
关键词：
神经母细胞瘤是一种高度异质性的恶性肿瘤，其结果广泛，从自然恶化到致命的化疗耐药疾病，目前根据儿童肿瘤学小组(COG)的风险分层进行治疗，由于缺乏治疗反应的预测因素，导致一些COG高危患者接受过度治疗。在这里，我们试图通过使用肿瘤细胞内微生物组来补充COG风险分类，这是肿瘤分子特征的一部分。我们确定，肿瘤内微生物基因丰度评分，即M-Score，将COG高危患者分为两个亚群(MHigh和Mlow)，其风险分层的准确性高于当前的COG风险评估，从而使一部分COG高危患者免于接受传统的高危治疗。目前，大多数神经母细胞瘤患者根据儿童肿瘤学小组(COG)的风险组分配进行治疗；然而，神经母细胞瘤的异质性使得治疗反应的预测因素很少，导致过度治疗。在这里，我们试图将COG风险分类与肿瘤细胞内微生物组相结合，这是肿瘤分子特征的一部分。我们确定，肿瘤内微生物基因丰度评分，即M-Score，将COG高危患者分为两个亚群(MHigh和Mlow)，其风险分层的准确性高于当前的COG风险评估，从而使一部分COG高危患者免于接受传统的高危治疗。从机制上讲，M-Score的分类能力意味着CREB的过度激活，可能影响与细胞增殖、抗凋亡和血管生成有关的关键基因，从而影响肿瘤细胞的增殖、存活和转移。因此，神经母细胞瘤中的细胞内微生物区系丰富，调节细胞内信号，从而影响患者的生存。
Neuroblastoma is a highly heterogeneous malignancy with a wide range of outcomes from spontaneous regression to fatal chemoresistant disease, as currently treated according to the risk stratification of the Children’s Oncology Group (COG), resulting in some high COG risk patients receiving excessive treatment, due to lacking predictors for treatment response. Here, we sought to complement COG risk classification by using the tumor intracellular microbiome, which is part of the tumor’s molecular signature. We determine that an intra-tumor microbial gene abundance score, namely M-score, separates the high COG-risk patients into two subpopulations (Mhigh and Mlow) with higher accuracy in risk stratification than the current COG risk assessment, thus sparing a subset of high COG-risk patients from being subjected to traditional high-risk therapies. Currently, most neuroblastoma patients are treated according to the Children’s Oncology Group (COG) risk group assignment; however, neuroblastoma’s heterogeneity renders only a few predictors for treatment response, resulting in excessive treatment. Here, we sought to couple COG risk classification with tumor intracellular microbiome, which is part of the molecular signature of a tumor. We determine that an intra-tumor microbial gene abundance score, namely M-score, separates the high COG-risk patients into two subpopulations (Mhigh and Mlow) with higher accuracy in risk stratification than the current COG risk assessment, thus sparing a subset of high COG-risk patients from being subjected to traditional high-risk therapies. Mechanistically, the classification power of M-scores implies the effect of CREB over-activation, which may influence the critical genes involved in cellular proliferation, anti-apoptosis, and angiogenesis, affecting tumor cell proliferation survival and metastasis. Thus, intracellular microbiota abundance in neuroblastoma regulates intracellular signals to affect patients’ survival.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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DOI：
10.1038/nrc3610
发表时间：
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期刊：
Nature reviews. Cancer
影响因子：
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