Li Chun-Yan, Li Bao-Xiu, Liang Yi, Peng Rui-Qing, Ding Ya, Xu Da-Zhi, Zhang Xin, Pan Zhi-Zhong, Wan De-Sen, Zeng Yi-Xin, Zhu Xiao-Feng, Zhang Xiao-Shi
Biotherapy Center,The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.
J Transl Med. 2009 Jul 7;7:56. doi: 10.1186/1479-5876-7-56.
Cancer stem cell model suggested that tumor progression is driven by the overpopulation of cancer stem cells and eradicating or inhibiting the symmetric division of cancer stem cells would become the most important therapeutic strategy. However, clinical evidence for this hypothesis is still scarce. To evaluate the overpopulation hypothesis of cancer stem cells the association of percentage of CD133+ tumor cells with clinicopathological parameters in colon cancer was investigated since CD133 is a putative cancer stem cell marker shared by multiple solid tumors.
Tumor tissues matched with adjacent normal tissues were collected from 104 stage IIIB colon cancer patients who were subject to radical resection between January, 1999 to July, 2003 in this center. The CD133 expression was examined with immunohistochemical staining. The correlation of the percentage of CD133+ cell with clinicopathological parameters and patients' 5-year survival was analyzed.
The CD133+ cells were infrequent and heterogeneous distribution in the cancer tissue. Staining of CD133 was localized not only on the glandular-luminal surface of cancer cells but also on the invasive budding and the poorly differentiated tumors with ductal structures. Both univariate and multivariate survival analysis revealed that the percentage of CD133+ cancer cells and the invasive depth of tumor were independently prognostic. The patients with a lower percentage of CD133+ cancer cells (less than 5%) were strongly associated with a higher 5-year survival rate than those with a higher percentage of CD133+ cancer cells (greater than or equal to 55%). Additionally, no correlation was obtained between the percentage of CD133+ cancer cells and the other clinicopathological parameters including gender, age, site of primary mass, pathologic types, grades, and invasive depth.
The fact that a higher percentage CD133+ cells were strongly associated with a poorer prognosis in patients with locally advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor progression, and the overpopulation hypothesis of cancer stem cell seems reasonable.
癌症干细胞模型表明,肿瘤进展是由癌症干细胞数量过多驱动的,根除或抑制癌症干细胞的对称分裂将成为最重要的治疗策略。然而,这一假设的临床证据仍然匮乏。为了评估癌症干细胞数量过多的假设,研究了结肠癌中CD133+肿瘤细胞百分比与临床病理参数之间的关联,因为CD133是多种实体瘤共有的一种假定癌症干细胞标志物。
收集了1999年1月至2003年7月在本中心接受根治性切除的104例IIIB期结肠癌患者的肿瘤组织及其相邻正常组织。采用免疫组织化学染色检测CD133表达。分析CD133+细胞百分比与临床病理参数及患者5年生存率的相关性。
CD133+细胞在癌组织中少见且分布不均。CD133染色不仅定位于癌细胞的腺腔表面,还定位于侵袭性芽生以及具有导管结构的低分化肿瘤。单因素和多因素生存分析均显示,CD133+癌细胞百分比和肿瘤浸润深度是独立的预后因素。CD133+癌细胞百分比低(低于5%)的患者与5年生存率较高密切相关,而CD133+癌细胞百分比高(大于或等于55%)的患者则相反。此外,CD133+癌细胞百分比与其他临床病理参数(包括性别、年龄、原发肿块部位、病理类型、分级和浸润深度)之间未发现相关性。
局部晚期结肠癌患者中CD133+细胞百分比越高与预后越差密切相关,这一事实表明CD133+癌细胞促进肿瘤进展,癌症干细胞数量过多的假设似乎合理。