Fu Yusi, Agrawal Swati, Snyder Daniel R, Yin Shiwei, Zhong Na, Grunkemeyer James A, Dietz Nicholas, Corlett Ryan, Hansen Laura A, Waddah Al-Refaie, Nandipati Kalyana C, Xia Jun
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, NE, USA.
Department of Surgery, Creighton University School of Medicine, Omaha, NE, USA.
Biomark Res. 2024 Aug 7;12(1):78. doi: 10.1186/s40364-024-00623-8.
The incidence of esophageal adenocarcinoma (EAC) has surged by 600% in recent decades, with a dismal 5-year survival rate of just 15%. Barrett's esophagus (BE), affecting about 2% of the population, raises the risk of EAC by 40-fold. Despite this, the transcriptomic changes during the BE to EAC progression remain unclear. Our study addresses this gap through comprehensive transcriptomic profiling to identify key mRNA signatures and genomic alterations, such as gene fusions. We performed RNA-sequencing on BE and EAC tissues from 8 individuals, followed by differential gene expression, pathway and network analysis, and gene fusion prediction. We identified mRNA changes during the BE-to-EAC transition and validated our results with single-cell RNA-seq datasets. We observed upregulation of keratin family members in EAC and confirmed increased levels of keratin 14 (KRT14) using immunofluorescence. More differentiated BE marker genes are downregulated during progression to EAC, suggesting undifferentiated BE subpopulations contribute to EAC. We also identified several gene fusions absent in paired BE and normal esophagus but present in EAC. Our findings are critical for the BE-to-EAC transition and have the potential to promote early diagnosis, prevention, and improved treatment strategies for EAC.
近几十年来，食管腺癌（EAC）的发病率激增了600%，其5年生存率低至仅15%，令人沮丧。巴雷特食管（BE）影响着约2%的人口，使EAC风险增加40倍。尽管如此，BE向EAC进展过程中的转录组变化仍不清楚。我们的研究通过全面的转录组分析来填补这一空白，以识别关键的mRNA特征和基因组改变，如基因融合。我们对8名个体的BE和EAC组织进行了RNA测序，随后进行了差异基因表达、通路和网络分析以及基因融合预测。我们确定了BE向EAC转变过程中的mRNA变化，并使用单细胞RNA测序数据集验证了我们的结果。我们观察到EAC中角蛋白家族成员上调，并通过免疫荧光证实角蛋白14（KRT14）水平升高。在向EAC进展过程中，更多分化的BE标记基因下调，表明未分化的BE亚群促成了EAC。我们还鉴定出在配对的BE和正常食管中不存在但在EAC中存在的几种基因融合。我们的发现对于BE向EAC的转变至关重要，并且有可能促进EAC的早期诊断、预防和改进治疗策略。
