Cancer stem cells biomarkers in gastric carcinogenesis.
Cancer stem cells biomarkers in gastric carcinogenesis.
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DOI：
10.1007/s12029-013-9534-2
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发表时间：
2013-12-01
影响因子：
1.6
通讯作者：
Majumdar, Adhip P N
中科院分区：
文献类型：
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作者：
Yang, Liu;Levi, Edi;Majumdar, Adhip P N
背景：胃癌的发生是一个多步骤的过程，涉及多种分子的改变，包括肿瘤干细胞的改变。本研究旨在通过检测胃癌发生不同阶段肿瘤干细胞的表达来确定肿瘤干细胞的变化是否可以作为胃癌发生进展的标志物。慢性浅表性胃炎（CSG）、慢性萎缩性胃炎（CAG）、或胃癌（GC）中的增殖细胞核抗原（PCNA）和Bcl-xl分别作为增殖和凋亡的生物标志物，并且通过qRT-PCR分析⑶ 44、⑶ 166和LGR 5水平作为胃CSC的标志物。此外，P53和磷酸化形式的表皮生长因子受体（p-EGFR）的水平进行了examined.RESULTS：而这些生物标志物的水平被发现是低至中度的CSG和CAG患者，他们显着增加，在GC患者，其中CD 44与LGR 5和CD 166与p-EGFR的共表达被发现是最高的。我们还观察到，尽管不同CSC标志物的表达以及p-EGFR水平在癌前病变中增加，结论：胃癌组织中的C-erbB-2蛋白表达与胃癌的发生、发展密切相关，C-erbB-2蛋白表达与胃癌的发生、发展密切相关。我们的观察表明，从癌前病变，如浅表性胃炎和慢性萎缩性胃炎，胃炎与CSC的诱导以及细胞增殖的增加和细胞凋亡的抑制有关。
BACKGROUND: Gastric carcinogenesis is a multistep process, involving multiple molecular alterations, including changes in cancer stem cells (CSCs). The present investigation was undertaken to determine whether changes in cancer stem cells could be utilized as a marker of progression of gastric carcinogenesis by examining the expression of gastric CSCs at different stages of carcinogenesis.METHODS: Ninety-three cases with 31 in each group of chronic superficial gastritis (CSG), chronic atrophic gastritis (CAG), or gastric cancer (GC) were analyzed immunohistochemically for proliferating cell nuclear antigen (PCNA) and Bcl-xl as biomarkers of proliferation and apoptosis, respectively, and CD44, CD166, and LGR5 levels by qRT-PCR as markers of gastric CSCs. Additionally, the levels of P53 and phosphorylated form of epidermal growth factor receptor (p-EGFR) were examined.RESULTS: While the levels of each of these biomarkers were found to be low to moderate in CSG and CAG patients, they were markedly increased in GC patients, in whom co-expression of CD44 with LGR5 and CD166 with p-EGFR was found to be the highest. We have also observed that although the expression of different CSC markers as well as the levels of p-EGFR were increased in precancerous lesions (CSG and CAG), they are further augmented in GC suggesting that they may play a pivotal role in the development and progression of gastric cancer.CONCLUSIONS: Our observations suggest that the progression to gastric carcinogenesis from preneoplastic lesions such as superficial gastritis and chronic atrophic gastritis is associated with induction of CSCs together with increase in cell proliferation and inhibition of apoptosis.