Stabenau Kaleigh A, Samuels Tina L, Lam Tina K, Mathison Angela J, Wells Clive, Altman Kenneth W, Battle Michele A, Johnston Nikki
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Laryngoscope. 2023 Jan;133(1):59-69. doi: 10.1002/lary.30109. Epub 2022 Mar 22.
At the conclusion of this presentation, participants should better understand the carcinogenic potential of pepsin and proton pump expression in Barrett's esophagus.
Barrett's esophagus (BE) is a well-known risk factor for esophageal adenocarcinoma (EAC). Gastric H /K ATPase proton pump and pepsin expression has been demonstrated in some cases of BE; however, the contribution of local pepsin and proton pump expression to carcinogenesis is unknown. In this study, RNA sequencing was used to examine global transcriptomic changes in a BE cell line ectopically expressing pepsinogen and/or gastric H /K ATPase proton pumps.
In vitro translational.
BAR-T, a human BE cell line devoid of expression of pepsinogen or proton pumps, was transduced by lentivirus-encoding pepsinogen (PGA5) and/or gastric proton pump subunits (ATP4A, ATP4B). Changes relative to the parental line were assessed by RNA sequencing.
Top canonical pathways associated with protein-coding genes differentially expressed in pepsinogen and/or proton pump expressing BAR-T cells included those involved in the tumor microenvironment and epithelial-mesenchymal transition. Top upstream regulators of coding transcripts included TGFB1 and ERBB2, which are associated with the pathogenesis and prognosis of BE and EAC. Top upstream regulators of noncoding transcripts included p300-CBP, I-BET-151, and CD93, which have previously described associations with EAC or carcinogenesis. The top associated disease of both coding and noncoding transcripts was cancer.
These data support the carcinogenic potential of pepsin and proton pump expression in BE and reveal molecular pathways affected by their expression. Further study is warranted to investigate the role of these pathways in carcinogenesis associated with BE.
NA Laryngoscope, 133:59-69, 2023.
在本报告结束时，参与者应能更好地理解胃蛋白酶和质子泵表达在巴雷特食管中的致癌潜力。
巴雷特食管（BE）是食管腺癌（EAC）的一个众所周知的危险因素。在一些BE病例中已证实存在胃H⁺/K⁺ ATP酶质子泵和胃蛋白酶表达；然而，局部胃蛋白酶和质子泵表达对致癌作用的贡献尚不清楚。在本研究中，RNA测序用于检查异位表达胃蛋白酶原和/或胃H⁺/K⁺ ATP酶质子泵的BE细胞系中的全局转录组变化。
体外翻译研究。
BAR-T是一种不表达胃蛋白酶原或质子泵的人BE细胞系，用编码胃蛋白酶原（PGA5）和/或胃质子泵亚基（ATP4A、ATP4B）的慢病毒进行转导。通过RNA测序评估相对于亲代细胞系的变化。
在表达胃蛋白酶原和/或质子泵的BAR-T细胞中差异表达的与蛋白质编码基因相关的顶级经典通路包括那些参与肿瘤微环境和上皮-间质转化的通路。编码转录本的顶级上游调节因子包括TGFB1和ERBB2，它们与BE和EAC的发病机制及预后相关。非编码转录本的顶级上游调节因子包括p300-CBP、I-BET-151和CD93，它们先前已被描述与EAC或致癌作用有关。编码和非编码转录本的顶级相关疾病均为癌症。
这些数据支持胃蛋白酶和质子泵表达在BE中的致癌潜力，并揭示了受其表达影响的分子途径。有必要进一步研究这些途径在与BE相关的致癌作用中的作用。
无 喉镜，133:59 - 69，2023年。
