H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer.
H. pylori infection is associated with DNA damage of Lgr5-positive epithelial stem cells in the stomach of patients with gastric cancer.
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DOI：
10.1007/s10620-012-2360-8
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发表时间：
2013-01
影响因子：
3.1
通讯作者：
Sepulveda, Antonia R.
中科院分区：
文献类型：
--
作者：
Uehara, Takeshi;Ma, Deqin;Yao, Yuan;Lynch, John P.;Morales, Knashawn;Ziober, Amy;Feldman, Michael;Ota, Hiroyoshi;Sepulveda, Antonia R.
幽门螺杆菌(Hp)感染是导致上皮细胞突变的胃癌发生的主要危险因素，并可能影响胃上皮干细胞。研究胃粘膜上皮干细胞标志物Lgr5的表达，探讨幽门螺杆菌(Hp)感染对Lgr5阳性上皮细胞(LPECs)的影响，以及LPECs对Hp感染相关DNA损伤的易感性。应用免疫组织化学和免疫荧光技术检测52例非肿瘤性胃黏膜组织中LGR5的表达，其中胃癌34例，非癌胃18例，幽门螺杆菌阳性21例，幽门螺杆菌阴性31例，HP−阳性31例。为了确定LPECs的DNA损伤程度，采用定量光谱分析的方法测定了氧化应激相关的DNA损伤标志物核8-羟基脱氧鸟苷(8OHdG)的含量。LPEC主要分布在胃窦部。胃癌组HP+组LPECs数显著高于HP-−非肿瘤组，P=0.006，而无胃癌组LPECs数无显著差异。8Hp+−患者LPECs中OHdG水平显著高于LGR5阴性上皮细胞(P=0.012)，而Hp-−患者Hp-LPECs中OHdG水平无显著差异(P=.414)，而无Gc患者Hp-LPECs与Hp-LGR5阴性上皮细胞间差异无统计学意义。幽门螺杆菌相关性胃炎患者胃窦部Lgr5阳性的上皮干细胞库扩大。在Hp感染活跃的GC患者中，LPECs可能比Lgr5阴性的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内的上皮干细胞而导致GC的风险。
H. pylori (Hp) infection is a main 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 stains. 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.
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影响因子：
29.4
作者：
Mills JC;Shivdasani RA
通讯作者：
Shivdasani RA
影响因子：
3.7
作者：
Simon E;Petke D;Böger C;Behrens HM;Warneke V;Ebert M;Röcken C
通讯作者：
Röcken C
影响因子：
120.7
作者：
MARSHALL, BJ
通讯作者：
MARSHALL, BJ
影响因子：
29.4
作者：
Sepulveda, Antonia R.;Yao, Yuan;Graham, David Y.
通讯作者：
Graham, David Y.
影响因子：
4.4
作者：
Yao, Yuan;Tao, Hong;Sepulveda, Antonia R.
通讯作者：
Sepulveda, Antonia R.