Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer.

Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer.
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DOI:
10.1038/sj.bjc.6605762
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发表时间:
2010-07-27
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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本研究的目的是阐明肿瘤干细胞标志物CD133、CD166、CD44s、EpCAM和乙醛脱氢酶-1(ALDH1)在结直肠癌中对预后的影响。对1420例原发结直肠癌和57例正常大肠黏膜组织芯片进行CD133、CD166、CD44s、EpCAM和ALDH1免疫组织化学染色,并与101例相应的全组织切片进行比较。检测了三株结直肠癌细胞系的侵袭能力。所有标记物在正常组织和癌组织之间均有差异(P<0.001)。单因素分析显示,CD166s和CD44s缺失与高PT(P=0.002,P=0.014)、高PN(P=0.004,P=0.002)、浸润性生长(P<0.001,P=0.002)和较差的生存(P=0.015,P=0.019)有关。膜型EPCAM表达缺失也与较高的PN(P=0.023)和浸润性生长方式(P=0.005)有关。CD44s、CD166和EpCAM的表达向侵袭前沿消失。3株结直肠癌细胞株的CD44−/CD16 6−细胞体外侵袭能力明显高于阳性细胞。膜性CD44s、CD166和EpCAM的缺失而不是过度表达与肿瘤进展有关。这支持了免疫组织化学对这些蛋白质的膜性评估可能代表了它们的细胞黏附而不是它们的细胞内功能的观点。
The aim of this study was to elucidate the prognostic impact of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and aldehyde dehydrogenase-1 (ALDH1) in colorectal cancer. A tissue microarray of 1420 primary colorectal cancers and 57 normal mucosa samples was immunostained for CD133, CD166, CD44s, EpCAM, and ALDH1 in addition to 101 corresponding whole tissue sections. Invasive potential of three colorectal cancer cell lines was tested. Differences between normal tissue and cancer were observed for all markers (P<0.001). Loss of membranous CD166 and CD44s were linked to higher pT (P=0.002, P=0.014), pN (P=0.004, P=0.002), an infiltrating growth pattern (P<0.001, P=0.002), and worse survival (P=0.015, P=0.019) in univariate analysis only. Loss of membranous EpCAM expression was also linked to higher pN (P=0.023) and infiltrating growth pattern (P=0.005). The CD44s, CD166, and EpCAM expression were lost towards the invasive front. The CD44−/CD166− cells from three colorectal cancer cell lines exhibited significantly higher invasive potential in vitro than their positive counterparts. Loss, rather than overexpression, of membranous CD44s, CD166, and EpCAM is linked to tumour progression. This supports the notion that the membranous evaluation of these proteins assessed by immunohistochemistry may be representative of their cell adhesion rather than their intra-cellular functions.
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