胃癌发生中推测的干细胞标志物的顺序表达。

Sequential expression of putative stem cell markers in gastric carcinogenesis.

机构信息

Cancer Science Institute, National University Health System and Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

出版信息

Br J Cancer. 2011 Aug 23;105(5):658-65. doi: 10.1038/bjc.2011.287. Epub 2011 Aug 9.

BACKGROUND

Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers.

METHODS

We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression.

RESULTS

We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy.

CONCLUSION

CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues.

背景

胃癌的发生过程已在逐步的组织病理学模型中得到充分证实，即 Correa 通路。已有研究报道 CD44、Musashi-1 和 CD133 等多种生物标志物可作为肿瘤干细胞（PSC）标志物。

方法

我们研究了 PSC 标志物 CD44、Musashi-1 和 CD133 的表达与胃癌的发生、预后和化疗反应的关系。对代表 Correa 通路不同阶段的胃癌（GC）临床标本进行免疫组织化学染色。还评估了经多西紫杉醇、顺铂和卡培他滨（DCX）新辅助化疗前后 GC 样本中 PSC 标志物的表达情况。

结果

与正常胃黏膜相比，GC 中三种 PSC 标志物的表达明显升高（每种标志物 P<0.001）。癌前病变，包括肠上皮化生和异型增生，CD44 和 Musashi-1 的表达增加。CD133 主要沿黏膜内癌和结缔组织之间的边界表达，在后期阶段更为明显。高 CD44 和 CD133 表达与患者生存预后较差相关（P=0.014 和 P=0.019）。少数高表达 CD44 和 CD133 的肿瘤对基于 DCX 的新辅助化疗有病理反应。