胃癌患者手术切除后 ABCG2 和 CD133 表达与预后的关系

Donghoon Kang, Jae Myeong Park, Sung-Hak Lee, Y. Cho, Bo-In Lee, Myung-Gyu Choi
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ABCG2 and CD133 expression levels were defined by intensity and dichotomized as medians. The associations among the expression levels of these markers, disease severity, and patient survival were also determined.Results: In the 411 patients for whom we analyzed the expression levels of these markers, 74.9% and 80.5% were found to have high levels of ABCG2 and CD133, respectively. High expression levels of ABCG2 and CD133 were more commonly observed in well-differentiated (p<0.001 and p=0.004, respectively) and intestinal lesions (p<0.001 and p=0.002, respectively). High ABCG2 expression correlated with improved survival outcomes, whereas high CD133 expression was associated with poorer outcomes. Cox regression analysis confirmed that stage, high ABCG2 (overall survival [OS]: hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41–0.91; p=0.015; recurrencefree survival [RFS]: HR, 0.55; 95% CI, 0.34–0.88; p=0.012), and CD133 expression (OS: HR, 1.59; 95% CI, 1.00–2.51; p=0.049; RFS: HR, 2.29; 95% CI, 1.21–4.34; p=0.011) were predictors of survival. 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摘要

目的:三磷酸腺苷结合盒亚家族G成员2 (ABCG2)和CD133是公认的胃癌干细胞标志物。广泛的研究已经检查了这些标志物在不同类型癌症中的重要性及其对预后的影响,将它们与各种肿瘤的不利临床结果联系起来。然而,这些标志物对胃癌的预后价值尚不清楚。我们研究ABCG2和CD133在胃癌组织中的表达及其与临床预后的关系。方法:采用免疫组织化学和组织芯片技术分析459例胃癌手术切除患者肿瘤样本中ABCG2和CD133的表达水平。ABCG2和CD133的表达水平以强度定义,并将其二分类为中位数。这些标志物的表达水平、疾病严重程度和患者生存之间的关系也被确定。结果:在我们分析这些标志物表达水平的411例患者中,74.9%和80.5%分别发现ABCG2和CD133高水平。ABCG2和CD133高表达多见于高分化(p<0.001和p=0.004)和肠道病变(p<0.001和p=0.002)。高ABCG2表达与改善的生存结果相关,而高CD133表达与较差的预后相关。Cox回归分析证实,高ABCG2期(总生存期[OS]:风险比[HR], 0.61;95%置信区间[CI], 0.41-0.91;p = 0.015;无复发生存期[RFS]: HR, 0.55;95% ci, 0.34-0.88;p=0.012), CD133表达(OS: HR, 1.59;95% ci, 1.00-2.51;p = 0.049;Rfs:每小时2.29;95% ci, 1.21-4.34;P =0.011)是生存的预测因子。亚组分析表明,在接受全身化疗的患者中,ABCG2的表达也与RFS率的提高有关。结论:肿瘤中ABCG2高表达和CD133低表达与胃癌切除术后患者生存改善相关,提示其作为预后生物标志物的潜在用途。
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Outcomes Associated With ABCG2 and CD133 Expression in Patients With Gastric Cancer After Surgical Resection
Objectives: Adenosine triphosphate-binding cassette subfamily G member 2 (ABCG2) and CD133 are recognized stem cell markers of gastric cancer. Extensive research has examined the significance of these markers in different types of cancers and their impact on prognoses, linking them to unfavorable clinical outcomes in various tumors. However, the prognostic value of these markers for gastric cancer remains unclear. We investigated the expression of ABCG2 and CD133 and their relationship with clinical outcomes in gastric cancer.Methods: ABCG2 and CD133 expression levels were analyzed, using immunohistochemistry and tissue microarrays, in tumor samples from 459 patients who underwent surgical resections due to gastric cancer. ABCG2 and CD133 expression levels were defined by intensity and dichotomized as medians. The associations among the expression levels of these markers, disease severity, and patient survival were also determined.Results: In the 411 patients for whom we analyzed the expression levels of these markers, 74.9% and 80.5% were found to have high levels of ABCG2 and CD133, respectively. High expression levels of ABCG2 and CD133 were more commonly observed in well-differentiated (p<0.001 and p=0.004, respectively) and intestinal lesions (p<0.001 and p=0.002, respectively). High ABCG2 expression correlated with improved survival outcomes, whereas high CD133 expression was associated with poorer outcomes. Cox regression analysis confirmed that stage, high ABCG2 (overall survival [OS]: hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.41–0.91; p=0.015; recurrencefree survival [RFS]: HR, 0.55; 95% CI, 0.34–0.88; p=0.012), and CD133 expression (OS: HR, 1.59; 95% CI, 1.00–2.51; p=0.049; RFS: HR, 2.29; 95% CI, 1.21–4.34; p=0.011) were predictors of survival. A subgroup analysis indicated that ABCG2 expression was also associated with an improved RFS rate in patients who received systemic chemotherapy.Conclusions: High ABCG2 expression and low CD133 expression in tumors correlated with improved survival outcomes in post-resection patients with gastric cancer, suggesting their potential utility as prognostic biomarkers.
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