乙醛脱氢酶1蛋白在浸润性乳腺癌患者原发灶与转移淋巴结中的表达及临床意义的研究
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摘要
乙醛脱氢酶1被报道为乳腺肿瘤干细胞的标记物之一，先前小样本报道显示乙醛脱氢酶1在乳腺癌原发灶中的表达和患者的不良预后相关。我们的试验力图研究乙醛脱氢酶1在其相对应的癌转移淋巴结中的表达是否也和患者的预后相关。分别检测ALDH1、ER、PR、HER-2和Ki-67在161例浸润性乳腺癌原发灶和癌转移淋巴结中的表达，并应用生存分析、一致性分析、单因素和多因素分析等统计学方法分析乙醛脱氢酶1的表达和患者临床预后的关系。
结果：
乳腺癌原发病灶表达乙醛脱氢酶1的患者较阴性患者相比拥有更短的无复发生存时间（P=0.004）和总生存时间（P=0.001）。癌转移淋巴结表达乙醛脱氢酶1的患者较阴性患者相比同样拥有更短的无复发生存时间（P=0.012）和总生存时间（P=0.008）。乙醛脱氢酶1在乳腺癌原发灶中表达在患者无复发生存和总生存的单因素和多因素分析中均有意义，其可能作为影响患者生存的独立影响因素之一。乙醛脱氢酶1在癌转移淋巴结中的表达在患者无复发生存和总生存的单因素分析中有意义，而在患者无复发生存和总生存的多因素分析中未显示出统计学意义（P>0.05）。
结论：（创新点）
1.我们通过一个较大的样本试验证实了乙醛脱氢酶1在乳腺癌原发病灶的表达不仅和患者的不良预后相关，而且乙醛脱氢酶1在乳腺癌原发灶中表达可作为影响乳腺癌患者生存和预后的独立影响因素之一。2.乙醛脱氢酶1在乳腺癌转移淋巴结中的表达虽然在患者无复发生存和总生存的多因素分析中暂未显示出统计学意义，但是其仍然显示出对评估患者预后的潜力。3.我们试验证实了乳腺肿瘤干细胞假说，乳腺癌细胞从原发病灶向淋巴结的转移可能源于乳腺肿瘤干细胞从原发病灶向淋巴结转移。4.乙醛脱氢酶1可作为乳腺肿瘤干细胞较可靠的标记物之一。
本实验受到吉林大学白求恩第一医院的白求恩B计划的资助[项目号：2012217]，实验的部分进展分别于2012和2013在美国圣安东尼奥全球乳腺癌大会（AmericanAssociation for Cancer Research，AACR）上进行了墙报展示，相关文章发表在“Pathology research and practice”SCI收录杂志（ImpactFactor:1.3）。
The enzyme aldehyde dehydrogenase1(ALDH1) has been reported as abiomarker for identifying cancer stem cells. Previous studies have shown thatALDH1expression in primary breast cancers was associated with poor clinicalprognosis. In this study, we aimed to determine whether ALDH1expression inaxillary lymph node metastases (ALNM) of breast cancer patients was alsoassociated with poor prognosis. Expression of ALDH1, ER, PgR, HER2andKi-67were examined in primary tumors and ALNM of161patients withinvasive breast cancer. Survival analysis and multivariate analysis were used todetermine the relationship between ALDH1expression and clinical prognosis.
Result:
Patients with positive ALDH1expression in primary tumors and in ALNMhad significantly shorter relapse-free survival (RFS) times and overall survival(OS) times compared to those whose tissues were ALDH1negative.ALDH1-positivity in primary tumors was significant both in univariate andmultivariate analyses of RFS (P=0.004) and OS (P=0.001). ALDH1expressionin ALNM was significant in a univariate analysis of RFS (P=0.012) and OS(P=0.008) but not in a multivariate analysis of RFS and OS (P>0.05).
Conclusion:
1. The expression of ALDH1in primary breast tumors or ALNM may beone potential risk factor for poor, long-term outcomes.2. Although ALDH1expression in ALNM was not significant in the multivariate analysis of RFS and OS,but it also has the great potential capacity in indicating prognosis.3.Weconfirmed the hypothesis of CSCs and suggest that the axillary lymph nodemetastases may be due to the metastases of CSCs.4.ALDH1is a reliablebiomarker of marking Breast cancer stem cells.
This work was supported by Norman Bethune Program of Jilin University[2012217]. Part of the experiment was respectively posted on the AmericanAssociation for Cancer Research on2012and2013.The related topic of thepaper was published on “Pathology research and practice”(SCI, ImpactFactor:1.3).
结果：
乳腺癌原发病灶表达乙醛脱氢酶1的患者较阴性患者相比拥有更短的无复发生存时间（P=0.004）和总生存时间（P=0.001）。癌转移淋巴结表达乙醛脱氢酶1的患者较阴性患者相比同样拥有更短的无复发生存时间（P=0.012）和总生存时间（P=0.008）。乙醛脱氢酶1在乳腺癌原发灶中表达在患者无复发生存和总生存的单因素和多因素分析中均有意义，其可能作为影响患者生存的独立影响因素之一。乙醛脱氢酶1在癌转移淋巴结中的表达在患者无复发生存和总生存的单因素分析中有意义，而在患者无复发生存和总生存的多因素分析中未显示出统计学意义（P>0.05）。
结论：（创新点）
1.我们通过一个较大的样本试验证实了乙醛脱氢酶1在乳腺癌原发病灶的表达不仅和患者的不良预后相关，而且乙醛脱氢酶1在乳腺癌原发灶中表达可作为影响乳腺癌患者生存和预后的独立影响因素之一。2.乙醛脱氢酶1在乳腺癌转移淋巴结中的表达虽然在患者无复发生存和总生存的多因素分析中暂未显示出统计学意义，但是其仍然显示出对评估患者预后的潜力。3.我们试验证实了乳腺肿瘤干细胞假说，乳腺癌细胞从原发病灶向淋巴结的转移可能源于乳腺肿瘤干细胞从原发病灶向淋巴结转移。4.乙醛脱氢酶1可作为乳腺肿瘤干细胞较可靠的标记物之一。
本实验受到吉林大学白求恩第一医院的白求恩B计划的资助[项目号：2012217]，实验的部分进展分别于2012和2013在美国圣安东尼奥全球乳腺癌大会（AmericanAssociation for Cancer Research，AACR）上进行了墙报展示，相关文章发表在“Pathology research and practice”SCI收录杂志（ImpactFactor:1.3）。
The enzyme aldehyde dehydrogenase1(ALDH1) has been reported as abiomarker for identifying cancer stem cells. Previous studies have shown thatALDH1expression in primary breast cancers was associated with poor clinicalprognosis. In this study, we aimed to determine whether ALDH1expression inaxillary lymph node metastases (ALNM) of breast cancer patients was alsoassociated with poor prognosis. Expression of ALDH1, ER, PgR, HER2andKi-67were examined in primary tumors and ALNM of161patients withinvasive breast cancer. Survival analysis and multivariate analysis were used todetermine the relationship between ALDH1expression and clinical prognosis.
Result:
Patients with positive ALDH1expression in primary tumors and in ALNMhad significantly shorter relapse-free survival (RFS) times and overall survival(OS) times compared to those whose tissues were ALDH1negative.ALDH1-positivity in primary tumors was significant both in univariate andmultivariate analyses of RFS (P=0.004) and OS (P=0.001). ALDH1expressionin ALNM was significant in a univariate analysis of RFS (P=0.012) and OS(P=0.008) but not in a multivariate analysis of RFS and OS (P>0.05).
Conclusion:
1. The expression of ALDH1in primary breast tumors or ALNM may beone potential risk factor for poor, long-term outcomes.2. Although ALDH1expression in ALNM was not significant in the multivariate analysis of RFS and OS,but it also has the great potential capacity in indicating prognosis.3.Weconfirmed the hypothesis of CSCs and suggest that the axillary lymph nodemetastases may be due to the metastases of CSCs.4.ALDH1is a reliablebiomarker of marking Breast cancer stem cells.
This work was supported by Norman Bethune Program of Jilin University[2012217]. Part of the experiment was respectively posted on the AmericanAssociation for Cancer Research on2012and2013.The related topic of thepaper was published on “Pathology research and practice”(SCI, ImpactFactor:1.3).
引文
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