Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

乳酸脱氢酶A在不同分级胃肠胰神经内分泌肿瘤中的表达及意义

目的:探讨乳酸脱氢酶A(lactate dehydrogenase A,LDHA)在不同病理分级的胃肠胰神经内分泌肿瘤(gastroenteropancreatic neuroendocrine tumors,GEP-NETs)患者组织中的表达及临床病理特征。方法:收集青岛大学附属医院2013年1月至2018年12月经内镜及手术切除的112例GEP-NETs患者的临床资料。根据肿瘤Ki-67增殖指数及核分裂像数分为G1级43例、G2级17例、G3级52例。通过免疫组织化学方法检测不同分级GEP-NETs组织中LDHA表达情况,并分析LDHA表达水平与患者临床病理特征、经典神经内分泌标志物、血清乳酸脱氢酶(lactate dehydrogenase,LDH)及生存预后的关系。采用χ2检验进行统计分析,Kaplan-Meier曲线进行生存分析,Log-rank检验进行生存分析组间比较。结果:不同病理分级GEP-NETs组织中的LDHA表达水平差异具有统计学意义(P<0.001),且分级越高,阳性表达率越高,G1、G2及G3级阳性表达率分别为48.8%、70.6%和86.5%。临床病理特征分析显示,LDHA在GEP-NETs中的表达与性别、肿瘤大小、TNM分期、浸润深度及淋巴结转移相关(均P<0.05)。KaplanMeier生存分析及Log-rank检验结果显示LDHA高表达患者生存率较低表达组差异具有统计学意义(P=0.005)。结论:LDHA表达水平在不同分级GEP-NETs患者存在差异,LDHA高表达提示患者预后不良。