The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer

Abstract

BackgroundExpression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC).MethodsA retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined.ResultsWe identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7% and 50.7% of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively).ConclusionsExpression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.

The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

“…We therefore consider CD133 to be an appropriate CSC marker. Previous studies investigated the relationship between ALDH1A1 and CD133 (18,26,27). The results of these studies differed.…”

“…A recent meta-analysis showed that the increased expression of ALDH1A1 is associated with poor OS and disease-free survival in lung cancer (5,(16)(17)(18)(19)). …”

Differential Expression of Cancer Stem Cell Markers ALDH1 and CD133 in Various Lung Cancer Subtypes

“…A significant reciprocal correlation was observed between expression of ALDH1 and CD133 (p = 0.001); thus we explored the cumulative staining patterns of theses markers and their association with clinicopathologic parameters in different subtypes of lung cancer. This method has been reported as the standard experimental practice by many investigators (29)(30)(31).…”

Comparative proteome analysis across non-small cell lung cancer cell lines

“…S100A2, an inducer and potential biomarker for NSCLC metastasis [37], showed high to very high expression in a subset of cell lines not harboring KRAS oncogene. Other examples of comprehensively quantified markers of poor clinical outcome included adenylate kinase 4 and aldehyde dehydrogenase 1A1 [38,39].…”