Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Founders 6, Philadelphia, PA 19104, USA.
Dig Dis Sci. 2013 Jan;58(1):140-9. doi: 10.1007/s10620-012-2360-8. Epub 2012 Sep 4.
H. pylori (Hp) infection is a major risk factor in gastric carcinogenesis leading to epithelial mutagenesis, and may affect gastric epithelial stem cells.
To characterize the expression of Lgr5, a marker of epithelial stem cells in human gastric mucosa, to determine whether Hp infection affects Lgr5-positive epithelial cells (LPECs) and whether LPECs are susceptible to DNA damage associated with Hp infection.
Lgr5 expression was characterized in non-neoplastic gastric mucosa from 52 patients (34 with and 18 without gastric cancer (GC); 21 Hp-positive (Hp+) and 31 Hp-negative (Hp-)) by immunohistochemical and immunofluorescence staining. To determine the extent of DNA damage in LPECs, nuclear 8-hydroxydeoxyguanosine (8OHdG), a marker of DNA damage associated with oxidative stress, was measured by quantitative spectral image analysis.
LPECs were primarily present in gastric antrum. Higher numbers of LPECs were seen in Hp+ than in Hp- non-neoplastic mucosa of GC patients, P = .006, but not in patients without GC. 8OHdG levels in LPECs were significantly higher than in Lgr5-negative epithelial cells in Hp+ GC patients (P = .012) but not in Hp- cases (P = .414), whereas no difference was seen between Hp+ and Hp- mucosa of patients without GC.
The Lgr5-positive epithelial stem cell pool is expanded in Hp-associated gastritis in the antrum of patients with GC. In GC patients with active Hp infection, LPECs may be more susceptible to DNA damage than Lgr5-negative epithelial cells, suggesting that Hp infection may contribute to GC risk by affecting epithelial stem cells in the human stomach.
幽门螺杆菌（Hp）感染是导致上皮突变和胃癌发生的主要危险因素，可能影响胃上皮干细胞。
描述人胃黏膜中上皮干细胞标志物 Lgr5 的表达，确定 Hp 感染是否影响 Lgr5 阳性上皮细胞（LPECs），以及 LPECs 是否易受与 Hp 感染相关的 DNA 损伤。
通过免疫组织化学和免疫荧光染色，对 52 例非肿瘤性胃黏膜（34 例胃癌患者，18 例无胃癌患者；21 例 Hp 阳性（Hp+），31 例 Hp 阴性（Hp-））进行 Lgr5 表达特征分析。为了确定 LPECs 中 DNA 损伤的程度，通过定量光谱图像分析测量核 8-羟基脱氧鸟苷（8OHdG），这是一种与氧化应激相关的 DNA 损伤标志物。
LPECs 主要存在于胃窦部。与 Hp-非肿瘤性胃黏膜相比，Hp+GC 患者的 Hp+非肿瘤性胃黏膜中 LPECs 数量更多，P=0.006，但在无 GC 患者中则不然。与 Hp-病例（P=0.414）相比，Hp+GC 患者的 LPECs 中 8OHdG 水平显著高于 Lgr5 阴性上皮细胞（P=0.012），而在 Hp-病例中则无差异。
在 GC 患者的 Hp 相关胃炎中，Lgr5 阳性上皮干细胞池在胃窦部扩张。在活动性 Hp 感染的 GC 患者中，LPECs 可能比 Lgr5 阴性上皮细胞更容易受到 DNA 损伤，这表明 Hp 感染可能通过影响人胃中的上皮干细胞而导致 GC 风险增加。
