Author:
Zhong Ying,Lin Yan,Shen Songjie,Zhou Yidong,Mao Feng,Guan Jinghong,Sun Qiang
Abstract
Abstract
Background
The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear.
Methods
147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated.
Results
ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman’s rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2-△△C T value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001).
Conclusions
The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference35 articles.
1. Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.
2. Ozbay T, Nahta R: Delphinidin inhibits HER2 and Erk1/2 signaling and suppresses growth of HER2-overexpressing and triple negative breast cancer cell lines. Breast Cancer. 2011, 5: 143-154.
3. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H: Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010, 28: 1684-1691. 10.1200/JCO.2009.24.9284.
4. Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111. 10.1038/35102167.
5. Kleer CG, Zhang Y, Pan Q, Gallagher G, Wu M, Wu ZF, Merajver SD: WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer. Breast Cancer Res. 2004, 6: R110-R115. 10.1186/bcr755.
Cited by
30 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献