Multi-omics analysis of adamantinomatous craniopharyngiomas reveals distinct molecular subgroups with prognostic and treatment response significance  

作　　者：Xianlong Wang Chuan Zhao Jincheng Lin Hongxing Liu Qiuhong Zeng Huadong Chen Ye Wang Dapeng Xu Wen Chen Moping Xu En Zhang Da Lin Zhixiong Lin 

机构地区：[1]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,Fujian 350122,China [2]Department of Neurosurgery,Sanbo Brain Hospital,Capital Medical University,Beijing 100093,China

出　　处：《Chinese Medical Journal》2024年第7期859-870,共12页中华医学杂志（英文版）

基　　金：Fujian Medical University(No.XRCZX2017001 to XW);Natural Science Foundation of Fujian Province(No.2019J01294 to XW);Sanbo Brain Hospital Management Group(No.SBJT-KY-2020-002 to ZL);Capital Health Research and Development Special Fund(No.2022-2-8013 to ZL)

摘　　要：Background:Adamantinomatous craniopharyngioma(ACP)is the commonest pediatric sellar tumor.No effective drug is available and interpatient heterogeneity is prominent.This study aimed to identify distinct molecular subgroups of ACP based on the multi-omics profiles,imaging findings,and histological features,in order to predict the response to anti-inflammatory treatment and immunotherapies.Methods:Totally 142 Chinese cases diagnosed with craniopharyngiomas were profiled,including 119 ACPs and 23 papillary craniopharyngiomas.Whole-exome sequencing(151 tumors,including recurrent ones),RNA sequencing(84 tumors),and DNA methylome profiling(95 tumors)were performed.Consensus clustering and non-negative matrix factorization were used for subgrouping,and Cox regression were utilized for prognostic evaluation,respectively.Results:Three distinct molecular subgroups were identified:WNT,ImA,and ImB.The WNT subgroup showed higher Wnt/β-catenin pathway activity,with a greater number of epithelial cells and more predominantly solid tumors.The ImA and ImB subgroups had activated inflammatory and interferon response pathways,with enhanced immune cell infiltration and more predominantly cystic tumors.Mitogen-activated protein kinases(MEK/MAPK)signaling was activated only in ImA samples,while IL-6 and epithelial-mesenchymal transition biomarkers were highly expressed in the ImB group,mostly consisting of children.The degree of astrogliosis was significantly elevated in the ImA group,with severe finger-like protrusions at the invasive front of the tumor.The molecular subgrouping was an independent prognostic factor,with the WNT group having longer event-free survival than ImB(Cox,P=0.04).ImA/ImB cases were more likely to respond to immune checkpoint blockade(ICB)therapy than the WNT group(P<0.01).In the preliminary screening of subtyping markers,CD38 was significantly downregulated in WNT compared with ImA and ImB(P=0.01).Conclusions:ACP comprises three molecular subtypes with distinct imaging and histological features.The prognosis

关 键 词：CRANIOPHARYNGIOMA Central nervous system tumor Precision medicine beta Catenin Proto-Oncogene Proteins B-raf 

分 类 号：R739.41[医药卫生—肿瘤]