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两种干细胞标志物,三磷酸腺苷结合盒,G2 亚家族(ABCG2)和 BMI-1,可预测口腔白斑癌变:一项长期随访研究。

Two stem cell markers, ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1, predict the transformation of oral leukoplakia to cancer: a long-term follow-up study.

机构信息

Department of Oral Mucosal Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, People's Republic of China.

出版信息

Cancer. 2012 Mar 15;118(6):1693-700. doi: 10.1002/cncr.26483. Epub 2011 Aug 25.

DOI:10.1002/cncr.26483
PMID:22009787
Abstract

BACKGROUND

Although oral leukoplakia (OL) is the best-known potentially malignant disorder, the risk of OL malignant transformation is difficult to assess. ATP-binding cassette, G2 subfamily (ABCG2) and BMI-1 are stem cell markers that have been found to be associated with head and neck tumorigenesis. The objective of the current study was to evaluate the usefulness of ABCG2 and BMI-1 in predicting OL transformation.

METHODS

In a retrospective cohort of 135 patients with OL from the study institution who had a mean follow-up of 5.5 years, 32 developed cancer between 1985 and 2008. The expression of ABCG2 and BMI-1 was determined using immunohistochemistry in samples from these patients, and included untransformed OL (n = 103) and malignant-transformed OL (n = 32). The association between protein expression and clinicopathological parameters and transformation was analyzed.

RESULTS

Expression of ABCG2 and BMI-1 was observed in 58 (43.0%) and 44 (32.6%) of 135 patients, respectively. The correlation between ABCG2 and BMI-1 expression was significant (P = .024). Kaplan-Meier analysis revealed that 37.9% of patients with ABCG2 positivity developed cancer compared with 13.0% of patients with ABCG2 negativity (P = .014, log-rank test). Approximately 40.9% of patients with BMI-1 positivity developed cancer compared with 15.4% of patients with BMI-1 negativity (P = .029, log-rank test). Multivariate analysis revealed that ABCG2 and BMI-1 expression was associated with a 3.24-fold (95% confidence interval [95% CI], 1.31-7.98; P = .011) and 4.03-fold (95% CI, 1.59-10.26; P = .003) increased the risk of transformation, respectively.

CONCLUSIONS

ABCG2 and BMI-1 expression was found to be associated with the development of oral cancer in a large cohort of patients with OL for whom long-term follow-up was available, which suggests that ABCG2 and BMI-1 may be used as predictors of OL transformation.

摘要

背景

尽管口腔白斑(OL)是最著名的潜在恶性疾病,但 OL 恶变的风险难以评估。ATP 结合盒,G2 亚家族(ABCG2)和 BMI-1 是已发现与头颈部肿瘤发生相关的干细胞标志物。本研究的目的是评估 ABCG2 和 BMI-1 在预测 OL 转化中的作用。

方法

在本机构回顾性队列中,有 135 例 OL 患者,平均随访 5.5 年,1985 年至 2008 年间有 32 例发生癌症。使用免疫组织化学法检测这些患者的 ABCG2 和 BMI-1 表达,并包括未转化的 OL(n = 103)和恶性转化的 OL(n = 32)。分析蛋白表达与临床病理参数和转化之间的关系。

结果

在 135 例患者中,分别有 58 例(43.0%)和 44 例(32.6%)表达 ABCG2 和 BMI-1。ABCG2 和 BMI-1 表达之间存在显著相关性(P =.024)。Kaplan-Meier 分析显示,ABCG2 阳性患者中有 37.9%发生癌症,而 ABCG2 阴性患者中仅有 13.0%发生癌症(P =.014,对数秩检验)。ABCG2 阳性患者中约有 40.9%发生癌症,而 BMI-1 阴性患者中仅有 15.4%发生癌症(P =.029,对数秩检验)。多变量分析显示,ABCG2 和 BMI-1 表达分别与 3.24 倍(95%置信区间[95%CI],1.31-7.98;P =.011)和 4.03 倍(95%CI,1.59-10.26;P =.003)的转化风险增加相关。

结论

在 OL 患者的大队列中,发现 ABCG2 和 BMI-1 的表达与口腔癌的发生相关,这些患者有长期随访,这表明 ABCG2 和 BMI-1 可作为 OL 转化的预测指标。

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