Laboratory of Genetic, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.
Dis Esophagus. 2012 Sep-Oct;25(7):638-44. doi: 10.1111/j.1442-2050.2011.01298.x. Epub 2012 Jan 11.
In the light of increasing evidence supporting cancer stem cells (CSCs) theory, the expression of two stem cell markers, CD133 and adenosine triphosphate-binding cassette superfamily G member 2 (ABCG2), in esophageal squamous cell carcinoma (ESCC) was investigated, and their prognostic values were evaluated. Paraffin-embedded tissue sections of 110 ESCC patients were investigated using Immunohistochemistry. The association of CD133 and ABCG2 expression with clinicopathologic characteristics was analyzed by χ(2) test. Survival analysis was carried out using Kaplan-Meier method and Cox proportional hazards model. CD133 and ABCG2 expression were detected in 27.3% and 15.5% of ESCC patients, respectively. The presence of CD133-positive cancer cells was associated with tumor cell differentiation (P= 0.008) but not significantly related to the survival of ESCC patients (P= 0.085). ABCG2 expression was not associated with clinicopathologic characteristics but was a significant prognostic factor for adverse overall survival of ESCC patients (P= 0.005). The median overall survival time for ESCC patients with and without ABCG2 expression were 21.8 and >49.3 months, respectively. A combined analysis of CD133 and ABCG2 expression did not show that ESCC patients with coexpression of these two markers had a worse prognosis than those with only ABCG2 expression (P= 0.934). Moreover, ABCG2 expression was revealed to be an independent prognostic factor along with tumor node metastasis stage in multivariate analysis (hazard ratio of ABCG2, 3.38; 95% confidence interval, 1.61∼7.09; P= 0.001). By survival analysis based on tumor node metastasis stage of ESCC, the association between ABCG2 expression and the patients' prognosis was found significant in the group of relatively early stage (P= 0.005) and marginally significant in the group of relatively late stage (P= 0.058). This is the first time to report the presence of CD133-positive cancer cells in ESCC but not supporting its prognostic value and validity as a CSC marker for ESCC. ABCG2 expression was found to correlate with the survival of ESCC patients, especially those at relatively early stage, suggesting that ABCG2-positive cancer cells may represent a pool of CSCs in ESCC, and relatively early-stage patients with ABCG2 expression may deserve more intensive or targeted therapy.
鉴于越来越多的证据支持癌症干细胞（CSC）理论，研究了两种干细胞标志物 CD133 和三磷酸腺苷结合盒超家族 G 成员 2（ABCG2）在食管鳞状细胞癌（ESCC）中的表达，并评估了它们的预后价值。使用免疫组织化学法检测了 110 例 ESCC 患者的石蜡包埋组织切片。通过卡方检验分析 CD133 和 ABCG2 表达与临床病理特征的关系。使用 Kaplan-Meier 方法和 Cox 比例风险模型进行生存分析。在 ESCC 患者中，分别检测到 27.3%和 15.5%的 CD133 和 ABCG2 表达。CD133 阳性癌细胞的存在与肿瘤细胞分化相关（P=0.008），但与 ESCC 患者的生存无显著相关（P=0.085）。ABCG2 表达与临床病理特征无关，但却是 ESCC 患者不良总生存的显著预后因素（P=0.005）。ESCC 患者中 CD133 和 ABCG2 表达阳性者的中位总生存时间分别为 21.8 个月和>49.3 个月。联合分析 CD133 和 ABCG2 表达并未显示同时表达这两种标志物的 ESCC 患者比仅表达 ABCG2 的患者预后更差（P=0.934）。此外，在多变量分析中，ABCG2 表达与肿瘤淋巴结转移分期一起被揭示为独立的预后因素（ABCG2 的风险比为 3.38；95%置信区间为 1.61∼7.09；P=0.001）。基于 ESCC 的肿瘤淋巴结转移分期的生存分析发现，ABCG2 表达与患者预后的相关性在相对早期组中具有显著意义（P=0.005），在相对晚期组中具有边缘显著意义（P=0.058）。这是首次报道 ESCC 中存在 CD133 阳性癌细胞，但不支持其作为 ESCC CSC 标志物的预后价值和有效性。ABCG2 表达与 ESCC 患者的生存相关，尤其是在相对早期的患者中，提示 ABCG2 阳性癌细胞可能代表 ESCC 中的 CSC 池，并且表达 ABCG2 的相对早期患者可能需要更密集或更有针对性的治疗。
