ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and p...ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and patient outcomes has not been evaluated until now.Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets.The association between ABCC8 and tumor immune cell infiltration,diverse gene mutation characteristics,tumor mutation burden(TMB),and survival in LGG was also investigated in several independent datasets.Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways.Through an online database,we found that ABCC8 expression in LGG was lower than in normal tissues.Then,the association of ABCC8 expression and immune cell infiltration in LGG was discussed.As we expected,the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets.Consistently,TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis.Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB.The high expression of ABCC8 was linked to improved survival of LGG patients.A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG.Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG.展开更多
Objective:Lower grade gliomas(LGGs),classified as World Health Organization(WHO)grade II and grade III gliomas,comprise a heterogeneous group with a median survival time ranging from 4–13 years.Accurate prediction of...Objective:Lower grade gliomas(LGGs),classified as World Health Organization(WHO)grade II and grade III gliomas,comprise a heterogeneous group with a median survival time ranging from 4–13 years.Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice.Methods:We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts.The comparative profile of immune genes was analyzed for signature identification and validation.In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas(CGGA)dataset were used as training and internal validation cohorts,respectively.The samples from The Cancer Genome Atlas(TCGA)and GSE16011 cohorts were used as external validation cohorts,and the real-time PCR of frozen LGG tissue samples(n=36)were used for clinical validation.Results:A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs(IGPs).A total of 402 IGPs were identified with prognostic values for LGGs.The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses.An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups,exhibiting different clinical outcomes.A nomogram,combining immune signature,1p/19q status,and tumor grade,was able to predict the overall survival(OS)with c-indices of 0.85,0.80,0.80,0.79,and 0.75 in the training,internal validation,external validation,and tissue sample cohorts,respectively.Conclusions:This study was the first to report a comparative profiling of immune genes in large LGG cohorts.A promising individualized immune signature was developed to estimate the survival time for LGG patients.展开更多
Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have tr...Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.展开更多
脑胶质瘤是脑实质最常见的原发恶性肿瘤。脑胶质瘤分为1~4级,其中2级和3级被称为较低级别脑胶质瘤(lower-grade gliomas,LGGs)。2021年世界卫生组织中枢神经系统分类(World Health Organization central nervous system,WHO CNS)深化了...脑胶质瘤是脑实质最常见的原发恶性肿瘤。脑胶质瘤分为1~4级,其中2级和3级被称为较低级别脑胶质瘤(lower-grade gliomas,LGGs)。2021年世界卫生组织中枢神经系统分类(World Health Organization central nervous system,WHO CNS)深化了分子分型对LGGs诊疗的重要性,以LGGs分子分型进行病理分级升级诊断。影像组学作为新兴领域,可术前无创预测LGGs分子分型,为LGGs的治疗评估及预后预测提供依据。目前已有较多研究通过分析MRI常规序列、功能序列,结合临床信息,运用机器学习和深度学习建立影像组学模型,术前无创预测LGGs分子分型。虽然其存在局限性,但仍具有一定的科研与临床意义。本文就LGGs分子分型在MRI影像组学的研究进展予以综述,以期通过MRI影像组学术前预测LGGs分子分型,便于指导临床个体化诊疗方案制订及预后预测。展开更多
脑胶质瘤是颅内最常见的恶性肿瘤,复发率高,预后较差。较低级别脑胶质瘤是指2021世界卫生组织中枢神经系统肿瘤分类(World Health Organization Central Nervous System,WHO CNS)分级为2级和3级的肿瘤,较低级别脑胶质瘤的分子分型对其...脑胶质瘤是颅内最常见的恶性肿瘤,复发率高,预后较差。较低级别脑胶质瘤是指2021世界卫生组织中枢神经系统肿瘤分类(World Health Organization Central Nervous System,WHO CNS)分级为2级和3级的肿瘤,较低级别脑胶质瘤的分子分型对其治疗与预后有着重要的指导意义,因此分子分型诊断对脑胶质瘤的临床管理至关重要。分子分型诊断的金标准是病理检测,获取病理组织基因测序,但其有一定的有创性和滞后性。近年来,随着功能磁共振成像(functional MRI,fMRI)的发展,越来越多的研究明确了fMRI预测较低级别胶质瘤分子分型的价值,本文就近年来多种fMRI技术,包括扩散成像、灌注成像、酰胺质子转移成像等,对预测较低级别胶质瘤多种分子分型的研究进展作一综述,并就各种fMRI技术对不同分子分型的预测价值分别进行分析,旨在为预测较低级别胶质瘤分子分型提供影像学指标,从而达到临床精准诊治的目的。展开更多
基金This work was supported by the Scientific and Technological Innovation Program for Clinical Medicine of Jinan(202019132)to LIPING GONG.
文摘ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and patient outcomes has not been evaluated until now.Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets.The association between ABCC8 and tumor immune cell infiltration,diverse gene mutation characteristics,tumor mutation burden(TMB),and survival in LGG was also investigated in several independent datasets.Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways.Through an online database,we found that ABCC8 expression in LGG was lower than in normal tissues.Then,the association of ABCC8 expression and immune cell infiltration in LGG was discussed.As we expected,the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets.Consistently,TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis.Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB.The high expression of ABCC8 was linked to improved survival of LGG patients.A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG.Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG.
基金This work was supported by grants from the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(Grant No.ZYLX201708)the National Natural Science Foundation of China(NSFC)/Research Grants Council(RGC)Joint Research Scheme(Grant No.81761168038)+3 种基金the Beijing Municipal Administration of Hospitals’Mission Plan(Grant No.SML20180501)the National Natural Science Foundation of China(Grant Nos.81672479,81802483,and 81872054)the National Postdoctoral Program for Innovative Talents(Grant No.BX20180384)the Liao Ning Revitalization Talents Program(Grant No.XLYC1807255).
文摘Objective:Lower grade gliomas(LGGs),classified as World Health Organization(WHO)grade II and grade III gliomas,comprise a heterogeneous group with a median survival time ranging from 4–13 years.Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice.Methods:We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts.The comparative profile of immune genes was analyzed for signature identification and validation.In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas(CGGA)dataset were used as training and internal validation cohorts,respectively.The samples from The Cancer Genome Atlas(TCGA)and GSE16011 cohorts were used as external validation cohorts,and the real-time PCR of frozen LGG tissue samples(n=36)were used for clinical validation.Results:A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs(IGPs).A total of 402 IGPs were identified with prognostic values for LGGs.The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses.An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups,exhibiting different clinical outcomes.A nomogram,combining immune signature,1p/19q status,and tumor grade,was able to predict the overall survival(OS)with c-indices of 0.85,0.80,0.80,0.79,and 0.75 in the training,internal validation,external validation,and tissue sample cohorts,respectively.Conclusions:This study was the first to report a comparative profiling of immune genes in large LGG cohorts.A promising individualized immune signature was developed to estimate the survival time for LGG patients.
文摘Lower-grade gliomas(including low-and intermediate-grade gliomas,World Health Organization grades II and III)are diffusely infiltrative neoplasms that arise most often in the cerebral hemispheres of adults and have traditionally been classified based on their presumed histogenesis as astrocytomas,oligodendrogliomas,or oligoastrocytomas.Although the histopathologic classification of lower-grade glioma has been the accepted standard for nearly a century,it suffers from high intra-and inter-observer variability and does not adequately predict clinical outcomes.Based on integrated analysis of multiplatform genomic data from The Cancer Genome Atlas,lower-grade gliomas have been found to segregate into three cohesive,clinically relevant molecular classes.Molecular classes were closely aligned with the status of isocitrate dehydrogenase(IDH)mutations,tumor protein 53 mutations and the co-deletion of chromosome arms 1 p and 19q,but were not closely aligned with histologic classes.These findings emphasize the potential for improved definition of clinically relevant disease subsets using integrated molecular approaches and highlight the importance of biomarkers for brain tumor classification.
文摘脑胶质瘤是脑实质最常见的原发恶性肿瘤。脑胶质瘤分为1~4级,其中2级和3级被称为较低级别脑胶质瘤(lower-grade gliomas,LGGs)。2021年世界卫生组织中枢神经系统分类(World Health Organization central nervous system,WHO CNS)深化了分子分型对LGGs诊疗的重要性,以LGGs分子分型进行病理分级升级诊断。影像组学作为新兴领域,可术前无创预测LGGs分子分型,为LGGs的治疗评估及预后预测提供依据。目前已有较多研究通过分析MRI常规序列、功能序列,结合临床信息,运用机器学习和深度学习建立影像组学模型,术前无创预测LGGs分子分型。虽然其存在局限性,但仍具有一定的科研与临床意义。本文就LGGs分子分型在MRI影像组学的研究进展予以综述,以期通过MRI影像组学术前预测LGGs分子分型,便于指导临床个体化诊疗方案制订及预后预测。
文摘脑胶质瘤是颅内最常见的恶性肿瘤,复发率高,预后较差。较低级别脑胶质瘤是指2021世界卫生组织中枢神经系统肿瘤分类(World Health Organization Central Nervous System,WHO CNS)分级为2级和3级的肿瘤,较低级别脑胶质瘤的分子分型对其治疗与预后有着重要的指导意义,因此分子分型诊断对脑胶质瘤的临床管理至关重要。分子分型诊断的金标准是病理检测,获取病理组织基因测序,但其有一定的有创性和滞后性。近年来,随着功能磁共振成像(functional MRI,fMRI)的发展,越来越多的研究明确了fMRI预测较低级别胶质瘤分子分型的价值,本文就近年来多种fMRI技术,包括扩散成像、灌注成像、酰胺质子转移成像等,对预测较低级别胶质瘤多种分子分型的研究进展作一综述,并就各种fMRI技术对不同分子分型的预测价值分别进行分析,旨在为预测较低级别胶质瘤分子分型提供影像学指标,从而达到临床精准诊治的目的。
