The Machine-Learning-Mediated Interface of Microbiome and Genetic Risk Stratification in Neuroblastoma Reveals Molecular Pathways Related to Patient Survival

作者全名："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"

作者地址："[Li, Xin; Stucky, Andres; Chen, Xuelian; Fletcher, Hansel; Wang, Charles; Zhong, Jiang] Loma Linda Univ, Sch Med, Dept Basic Sci, Loma Linda, CA 92350 USA; [Wang, Xiaoqi; Huang, Ruihao; Wen, Qin; Zeng, Yunjing; Zhang, Xi] Army Med Univ, Xinqiao Hosp, Med Ctr Hematol, State Key Lab Trauma Burn & Combined Injury, Chongqing 400037, Peoples R China; [Sun, Lan] Chongqing Med Univ, Peoples Hosp Bishan Dist, Dept Oncol, Bishan Hosp, Chongqing 400037, Peoples R China; [Xu, Yi; Cao, Huynh] Loma Linda Univ, Dept Med, Div Hematol & Oncol, Loma Linda, CA 92350 USA; [Xu, Yi; Cao, Huynh] Loma Linda Univ, Dept Med, Div Regenerat Med, Loma Linda, CA 92350 USA; [Xu, Yi; Cao, Huynh; Zhong, Jiang] Loma Linda Univ, Canc Ctr, Loma Linda, CA 92350 USA; [Sun, Fengzhu] Univ Southern Calif, Quantitat & Computat Biol Dept, Los Angeles, CA 90089 USA; [Li, Shengwen Calvin] Childrens Hosp Orange Cty CHOC, CHOC Childrens Res Inst, 1201 La Veta Ave, Orange, CA 92868 USA; [Li, Shengwen Calvin] Univ Calif Irvine, Sch Med, Dept Neurol, 200 S Manchester Ave,Ste 206, Orange, CA 92868 USA"

通信作者："Zhong, J (通讯作者)，Loma Linda Univ, Sch Med, Dept Basic Sci, Loma Linda, CA 92350 USA.; Zhang, X (通讯作者)，Army Med Univ, Xinqiao Hosp, Med Ctr Hematol, State Key Lab Trauma Burn & Combined Injury, Chongqing 400037, Peoples R China.; Zhong, J (通讯作者)，Loma Linda Univ, Canc Ctr, Loma Linda, CA 92350 USA.; Li, SC (通讯作者)，Childrens Hosp Orange Cty CHOC, CHOC Childrens Res Inst, 1201 La Veta Ave, Orange, CA 92868 USA.; Li, SC (通讯作者)，Univ Calif Irvine, Sch Med, Dept Neurol, 200 S Manchester Ave,Ste 206, Orange, CA 92868 USA."

来源：CANCERS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000815984200001

JCR分区：Q2

影响因子：5.2

年份：2022

卷号：14

期号：12

开始页：　

结束页：　

文献类型：Article

关键词：neuroblastoma; genetic risk stratification; machine learning; microbial-based cancer prognosis; RNA-seq; microbial signature

摘要："Simple Summary 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 (M-high and M-low) 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 (M-high and M-low) 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."

基金机构："National Institutes of Health (NCI) [R01 CA197903, R01 CA251848]; CHOC Children's-UC Irvine Child Health Research Awards [16004004]; CHOCUCI Child Health Research grant [16004003]; Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX1063]; Major project of Chongqing Science and Health Joint Medical Research Project [2022DBXM003]; Natural Science Foundation of Chongqing Innovation Group Science Program [cstc2021jcyj-cxttX0001001]"

基金资助正文："This work was supported in part by the National Institutes of Health (NCI, R01 CA197903 & R01 CA251848); CHOC Children's-UC Irvine Child Health Research Awards #16004004; CHOCUCI Child Health Research grant #16004003; Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX1063]; Major project of Chongqing Science and Health Joint Medical Research Project (2022DBXM003); and Natural Science Foundation of Chongqing Innovation Group Science Program (cstc2021jcyj-cxttX0001001)."