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

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.

The prognostic significance of ALDH1A1 expression in early invasive breast cancer

“…42,43 Domenic et al 44 reported that SOX9 expression may maintain human breast luminal progenitor cells, and may be associated with more aggressive tumours in BC. 45 The results of this study indicate that ALDH1A1 may be used not only as a CSC marker, but also as a prognostic and predictive marker, in BC. The protein expression of ALDH1A1 was more frequent in the highly proliferative (luminal B and TNBC) tumours, which suggests that ALDH1A1 may contribute to cell proliferation and tumorigenesis of BC.…”

“…The downstream genes of the retinoic acid pathway are also involved in the differentiation and proliferation of tumour cells. 45 The study results demonstrate that high expression of ALDH1A1 at both protein and mRNA levels has a positive association with poor prognostic features. Fei et al 39 concluded that ALDH1A1 predicts patient outcome in TNBC.…”

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

“…Additionally, when we included ALDH1A1 expression in the signature, EpCAM high VIM low ALDH1A1 high , its outcome prediction potential power was improved, remarking the need for the study of more cells markers besides EpCAM. In addition to its association with therapy failure, ALDH1A1 expression in tissue samples has been related to poor prognosis in different BC subtypes [63][64][65][66], and its expression in CTCs has also been linked with worse outcome in BC patients [23,26,28,32,67]. Likewise, Keup and colleagues suggested that the use of novel agents to attack BC stem cells, like salinomycin and a new synthetic curcumin analog against Aldehyde Dehydrogenase 1 (ALDH1), could be promising in patients with ALDH1+ CTCs [27].…”

212Pb-Labeled Antibody 225.28 Targeted to Chondroitin Sulfate Proteoglycan 4 for Triple-Negative Breast Cancer Therapy in Mouse Models

“…Standard chemotherapies (e.g., taxanes) have been shown to enrich the population of CICs in TNBC [ 7 , 8 , 9 ]. These surviving CICs are implicated in generating chemotherapy-resistant, recurrent, and metastatic disease [ 1 , 3 , 10 ]. Therefore, there is a clinical need to develop novel, targeted approaches that kill both differentiated TNBC cells and CICs, particularly in recurrent and metastatic lesions, to improve the outcomes for patients with TNBC.…”