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醛脱氢酶1的表达与乳腺癌的不良预后相关。

Aldehyde dehydrogenase 1 expression is correlated with poor prognosis in breast cancer.

作者信息

Yao Juan, Jin Qin, Wang Xu-Dong, Zhu Hui-Jun, Ni Qi-Chao

机构信息

Department of Pathology, Affiliated Hospital of Nantong University, Nantong Department of Pathology, Huaiyin Hospital of Huai'an city, Huai'an Department of Laboratory Medicine Department of Clinical Tissue Bank Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Medicine (Baltimore). 2017 Jun;96(25):e7171. doi: 10.1097/MD.0000000000007171.

Abstract

Breast cancer (BC) is one of the most common cancers worldwide, and is a major cause of death in women. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells and cancer stem cells, and its activity correlates with the outcome of various tumors, including BC. This study aimed to analyze the relationship between ALDH1 expression and clinicopathological characters in BC and the prognostic significance of ALDH1.We used quantitative reverse-transcription PCR (qRT-PCR) to detect ALDHA1 mRNA levels in 25 fresh frozen BC samples and matched noncancerous samples. Immunohistochemistry on tissue microarrays was used to analyze protein expression in 137 paraffin-embedded BC tissues and corresponding noncancerous tissues. STATA 16.0 software was used for statistical analysis.The results suggested that levels of both ALDH1 mRNA and protein in BC were significantly higher than in corresponding adjacent breast samples (3.856 ± 0.3442 vs 1.385 ± 0.1534, P < .001; 52.6% vs 25.5%, P < .001, respectively). ALDH1 protein expression was also significantly associated with histological grade (P  =  .017), tumor size (P  =  .017), and tumor-node-metastasis (TNM) stage (P  =  .038). Multivariate analysis using the Cox regression model demonstrated that ALDH1 expression (P  =  .024), molecular typing (P  =  .046), and TNM classification (P  =  .034) were independent predictive factors for the outcome of BC. Kaplan-Meier analysis and the log-rank test indicated that patients with high ALDH1 expression, triple-negative BC, and advanced TNM stage had a reduced overall survival time.These data suggest that ALDH1 could be used as a prognostic factor for BC and may provide a useful therapeutic target in the treatment of BC.

摘要

乳腺癌(BC)是全球最常见的癌症之一,也是女性死亡的主要原因。醛脱氢酶1(ALDH1)是干细胞和癌症干细胞的标志物,其活性与包括BC在内的各种肿瘤的预后相关。本研究旨在分析BC中ALDH1表达与临床病理特征之间的关系以及ALDH1的预后意义。我们使用定量逆转录PCR(qRT-PCR)检测25份新鲜冷冻BC样本和配对的癌旁样本中ALDHA1 mRNA水平。采用组织芯片免疫组化分析137份石蜡包埋BC组织及相应癌旁组织中的蛋白表达。使用STATA 16.0软件进行统计分析。结果表明,BC中ALDH1 mRNA和蛋白水平均显著高于相应的乳腺相邻样本(分别为3.856±0.3442 vs 1.385±0.1534,P<0.001;52.6% vs 25.5%,P<0.001)。ALDH1蛋白表达也与组织学分级(P = 0.017)、肿瘤大小(P = 0.017)和肿瘤-淋巴结-转移(TNM)分期(P = 0.038)显著相关。使用Cox回归模型进行多因素分析表明,ALDH1表达(P = 0.024)、分子分型(P = 0.046)和TNM分类(P = 0.034)是BC预后的独立预测因素。Kaplan-Meier分析和对数秩检验表明,ALDH1高表达、三阴性BC和晚期TNM分期的患者总生存时间缩短。这些数据表明,ALDH1可作为BC的预后因素,可能为BC治疗提供有用的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccdf/5484203/22dfbc71454b/medi-96-e7171-g001.jpg

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