Zeng Yongji, Li Qing K, Roy Sujayita, Mills Jason C, Jin Ramon U
Section of Gastroenterology, Department of Medicine, Baylor College of Medicine, Houston, TX, United States.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, United States.
Front Cell Dev Biol. 2023 Mar 13;11:1151790. doi: 10.3389/fcell.2023.1151790. eCollection 2023.
Plasticity is an inherent property of the normal gastrointestinal tract allowing for appropriate response to injury and healing. However, the aberrancy of adaptable responses is also beginning to be recognized as a driver during cancer development and progression. Gastric and esophageal malignancies remain leading causes of cancer-related death globally as there are limited early disease diagnostic tools and paucity of new effective treatments. Gastric and esophageal adenocarcinomas share intestinal metaplasia as a key precancerous precursor lesion. Here, we utilize an upper GI tract patient-derived tissue microarray that encompasses the sequential development of cancer from normal tissues to illustrate the expression of a set of metaplastic markers. We report that in contrast to gastric intestinal metaplasia, which has traits of both incomplete and complete intestinal metaplasia, Barrett's esophagus (i.e., esophageal intestinal metaplasia) demonstrates hallmarks of incomplete intestinal metaplasia. Specifically, this prevalent incomplete intestinal metaplasia seen in Barrett's esophagus manifests as concurrent development and expression of both gastric and intestinal traits. Additionally, many gastric and esophageal cancers display a loss of or a decrease in these characteristic differentiated cell properties, demonstrating the plasticity of molecular pathways associated with the development of these cancers. Further understanding of the commonalities and differences governing the development of upper GI tract intestinal metaplasias and their progression to cancer will lead to improved diagnostic and therapeutic avenues.
可塑性是正常胃肠道的固有特性，使其能够对损伤和愈合做出适当反应。然而，适应性反应的异常也开始被认为是癌症发生和发展的驱动因素。胃癌和食管癌仍然是全球癌症相关死亡的主要原因，因为早期疾病诊断工具有限，且缺乏新的有效治疗方法。胃腺癌和食管腺癌都有肠化生作为关键的癌前病变。在此，我们利用一种来自上消化道患者的组织微阵列，该微阵列涵盖了从正常组织到癌症的连续发展过程，以说明一组化生标志物的表达情况。我们报告称，与具有不完全和完全肠化生特征的胃肠化生不同，巴雷特食管（即食管肠化生）表现出不完全肠化生的特征。具体而言，在巴雷特食管中常见的这种不完全肠化生表现为胃和肠特征的同时发展和表达。此外，许多胃癌和食管癌显示出这些特征性分化细胞特性的丧失或减少，这表明与这些癌症发展相关的分子途径具有可塑性。进一步了解上消化道肠化生发展及其向癌症进展的共性和差异，将有助于改善诊断和治疗途径。
