Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients.
Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients.
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DOI：
10.1186/1756-9966-31-71
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发表时间：
2012-09-11
期刊：
影响因子：
--
通讯作者：
Sgambato A
中科院分区：
文献类型：
--
作者：
Coco C;Zannoni GF;Caredda E;Sioletic S;Boninsegna A;Migaldi M;Rizzo G;Bonetti LR;Genovese G;Stigliano E;Cittadini A;Sgambato A
先前已报道，CD 133（一种癌症干细胞标志物）和肌营养不良蛋白聚糖（α-DG）复合物α-亚基的表达水平在结直肠癌中发生改变。采用免疫组化方法检测CD 133和α-DG在结肠癌组织中的表达水平，并分析其与预后的关系。在正常结肠粘膜的隐窝底部很少检测到CD 133阳性的分散细胞，而在癌细胞中，阳性细胞的中位百分比为5%（范围0-80）。pT参数与肿瘤分期显著相关，但与肿瘤分级和N状态无关。在CD 133高表达肿瘤中，疾病复发和死亡的发生率显著更高，Kaplan-Meier曲线显示高表达组与低表达组之间无病生存期（p = 0.002）和总生存期（p = 0.008）的显著分离。α-DG的表达在相当一部分肿瘤中减少，但低α-DG染色与任何经典的临床病理参数无关。α-DG低表达肿瘤的复发和死亡率显著更高，Kaplan-Meier曲线显示高表达肿瘤与低表达肿瘤的无病生存期（p = 0.02）和总生存期（p = 0.02）显著分离。多变量分析证实，CD 133表达增加（而非α-DG丢失）是与复发（RR = 2.4; p = 0.002）和死亡（RR = 2.3; p = 0.003）风险增加相关的独立预后参数。α-DG缺失和CD 133表达增加是结肠癌的常见事件，对CD 133表达的评估有助于识别高危结肠癌患者。
Expression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers. Expression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated. Scattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0–80). A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002) and overall (p = 0.008) survival. Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002) and death (RR = 2.3; p = 0.003). Loss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.
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