背景:肺发育不全导致先天性膈疝(CDH)相关的发病率和死亡率。肺无翼型MMTV整合位点家族成员(Wnt)信号及其下游效应β-连环蛋白(CTNNB1)的变化,作为转录共激活因子,存在于动物CDH模型中,但在人类中没有很好的表征。我们旨在鉴定人CDH肺中Wnt信号传导基因表达的变化,并假设途径表达将低于对照。
方法:我们在2012年至2022年期间用福尔马林固定石蜡包埋(FFPE)尸检肺组织鉴定了51例CDH病例和10例非CDH对照。研究中排除了11例活出生CDH病例和另外2例前膈疝。留下38例CDH病例。测定19例CDH病例和9例对照的Wnt信号传导效应子WNT2B和CTNNB1的信使核糖核酸(mRNA)表达。对CDH病例和对照肺切片的子集进行β-连环蛋白免疫染色。从尸检报告中获得临床变量。
结果:中位胎龄为21周。81%(n=31)的疝气为左侧。47%(n=18)为后外侧。81%(n=31)的病例中肝脏位置上升。根据尸检照片,58%(n=22)的病例的缺陷大小为C型或D型,在42%(n=16)的病例中无法确定。CDH和非CDH肺之间的WNT2B和CTNNB1mRNA表达没有差异。CDH肺表达β-连环蛋白的间质细胞少于非CDH肺(13.2%vs42.4%;p=0.006)。
结论:CDH和非CDH肺之间β-catenin蛋白的丰度和/或定位似乎存在差异。
方法:三级。
方法:病例对照研究。
BACKGROUND: Lung hypoplasia contributes to congenital diaphragmatic hernia (CDH) associated morbidity and mortality. Changes in lung wingless-type MMTV integration site family member (Wnt)-signalling and its downstream effector beta-catenin (CTNNB1), which acts as a transcription coactivator, exist in animal CDH models but are not well characterized in humans. We aim to identify changes to Wnt-signalling gene expression in human CDH lungs and hypothesize that pathway expression will be lower than controls.
METHODS: We identified 51 CDH cases and 10 non-CDH controls with archival formalin-fixed paraffin-embedded (FFPE) autopsy lung tissue from 2012 to 2022. 11 liveborn CDH cases and an additional two anterior diaphragmatic hernias were excluded from the study, leaving 38 CDH cases. Messenger ribonucleic acid (mRNA) expression of Wnt-signalling effectors WNT2B and CTNNB1 was determined for 19 CDH cases and 9 controls. A subset of CDH cases and controls lung sections were immunostained for β-catenin. Clinical variables were obtained from autopsy
reports.
RESULTS: Median gestational age was 21 weeks. 81% (n = 31) of hernias were left-sided. 47% (n = 18) were posterolateral. Liver position was up in 81% (n = 31) of cases. Defect size was Type C or D in 58% (n = 22) of cases based on autopsy photos, and indeterminable in 42% (n = 16) of cases. WNT2B and CTNNB1 mRNA expression did not differ between CDH and non-CDH lungs. CDH lungs had fewer interstitial cells expressing β-catenin protein than non-CDH lungs (13.2% vs 42.4%; p = 0.006).
CONCLUSIONS: There appear to be differences in the abundance and/or localization of β-catenin proteins between CDH and non-CDH lungs.
METHODS: Level III.
METHODS: Case-Control Study.