Abstract
BackgroundAldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer. However, the clinicopathological and prognostic significance of this protein in breast cancer patients remains controversial.MethodsThis meta-analysis was conducted to address the above issues using 15 publications covering 921 ALDH1A1+ cases and 2353 controls. The overall and subcategory analyses were performed to detect the association between ALDH1A1 expression and clinicopathological/prognostic parameters in breast cancer patients.ResultsThe overall analysis showed that higher expression of ALDH1A1 is associated with larger tumor size, higher histological grade, greater possibility of lymph node metastasis (LNM), higher level expression of epidermal growth factor receptor 2 (HER2), and lower level expression of estrogen receptor (ER)/progesterone receptor (PR). The prognosis of breast cancer patients with ALDH1A1+ tumors was poorer than that of the ALDH1A1- patients. Although the relationships between ALDH1A1 expression and some clinicopathological parameters (tumor size, LNM, and the expression of HER2) was not definitive to some degree when we performed a subcategory analysis, the predictive values of ALDH1A1 expression for histological grade and survival of breast cancer patients were significant regardless of the different cutoff values of ALDH1A1 expression, the different districts where the patients were located, the different clinical stages of the patients, the difference in antibodies used in the studies, and the surgery status.ConclusionsOur results indicate that ALDH1A1 is a biomarker to predict tumor progression and poor survival of breast cancer patients. This marker should be taken into consideration in the development of new diagnostic and therapeutic program for breast cancer.
Highlights
Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer
We identified the detected subtype as ALDH1A1 based on the antibodies listed in the references
The prognostic data from Lee et al [26] was not available, because it was evaluated according to the change of expression of ALDH1A1 before and after the chemotherapy, rather than the categories ALDH1A1+ and ALDH1A1−
Summary
Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer. Since the first report of these cells, which were found among acute myeloid leukemia cells by cell sorting technology using multiple surface markers [4], CSCs have been reported in various tumors, such as colon cancer [5], brain tumor [6], and lung cancer [7]. Due to their high tumorigenic and metastatic potential, CSCs are thought to be the most formidable obstacle to the successful treatment of cancer. Ginestier et al have reported that the activity of aldehyde dehydrogenase 1 (ALDH1) as assessed by the Aldefluor assay is a specific indicator for identifying, isolating, and tracking human breast CSCs [11]
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