Zhang Ying, Wang Hu, Bi Chao, Xiao Yinping, Liu Zhaoyong
Department of Pathology, Shantou University Medical College, Shantou, Guangdong Province, China.
Department of Orthopaedics, First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province, China.
Oncotarget. 2016 Aug 23;7(34):54973-54982. doi: 10.18632/oncotarget.10362.
Gastric cardia cancer (GCC) is located in the distal stomach, and strongly correlates with atrophic gastritis and Helicobacter pylori (H.pylori) infection. Caudal-related homeobox transcription factor 2 (CDX2) is homeobox gene encoding an intestine-specific transcription factor usually expressed in the intestinal epithelium cells. However, in several recent published papers, CDX2 was found to be aberrantly expressed in gastric, thyroid and ovarian cancer.
Higher expression of CDX2 was found in GCC tissues in comparison with non-malignant cardia mucosa (p<0.05). Moreover, immunohistochemical analysis demonstrated that CDX2 expression correlated with lymphatic metastasis. In addition, we found that CDX2 expression progressively increased with the level of H. pylori infection (p<0.05), and also correlated with cell proliferation, based on Ki67 staining.
To investigate the relationship between CDX2, cell proliferation and H. pylori infection, we detected CDX2, Ki62 and H.pylori expression in 83 non-malignant gastric cardia mucosacases and 60 GCC specimens in the Chaoshan area, a high-risk region for esophageal and gastric cardia cancer.
These findings provide pathological evidence that H. pylori infectionis a driving force of gastric cardia carcinogenesis by upregulating CDX2 and inducing inflammation. These results provide new pathological evidence that H. pylori infection induces GCC tumorigenesis.
贲门癌(GCC)位于胃远端,与萎缩性胃炎和幽门螺杆菌(H.pylori)感染密切相关。尾型相关同源框转录因子2(CDX2)是一种同源框基因,编码一种通常在肠上皮细胞中表达的肠道特异性转录因子。然而,在最近发表的几篇论文中,发现CDX2在胃癌、甲状腺癌和卵巢癌中异常表达。
与非恶性贲门黏膜相比,GCC组织中CDX2表达更高(p<0.05)。此外,免疫组化分析表明CDX2表达与淋巴转移相关。另外,我们发现基于Ki67染色,CDX2表达随H.pylori感染水平的升高而逐渐增加(p<0.05),且也与细胞增殖相关。
为了研究CDX2、细胞增殖与H.pylori感染之间的关系,我们检测了潮汕地区83例非恶性贲门胃黏膜病例和60例GCC标本中CDX2、Ki62和H.pylori的表达,潮汕地区是食管癌和贲门癌的高发区。
这些发现提供了病理学证据,表明H.pylori感染通过上调CDX2和诱导炎症,是贲门癌发生的驱动力。这些结果为H.pylori感染诱导GCC肿瘤发生提供了新的病理学证据。