Overexpression of ALDH1A1 is associated with poor prognosis and therapeutic effects of sulforaphane in esophageal cancer

Human esophageal cancer is one of the most common causes of cancer death in China. Tumor recurrence and metastasis are the main reasons for the failure in cancer treatments. Increasing evidences indicated that cancer stem cell (CSC) are thought to be responsible for tumor initiation and progression. Therefore, therapies targeting cancer stem cells offer a promising strategy for cancer treatment. In this study, we not only evaluated ALDH1A1 level in esophageal cancer and stromal cells, but also studied therapeutic effects of Sulforaphane on ALDH1A1+ cancer stem like cells. Immunohistochemical analysis indicated that 66% (66/100) primary lesions exhibited positive staining for tumor cell ALDH1A1 expression. For another, strong stromal ALDH1A1 expression was also observed in 56% (56/100) cases. Clinicopathological relevance analysis showed ALDH1A1 expression in tumor cells was significantly correlated with lymph node metastasis, Stage and poor prognosis. While high stromal expression of ALDH1A1 was significantly associated with better overall survival. According to the efficacy of Sulforaphane on inhibiting CSC, we examined whether it could eradicate the ALDH1A1-positive esophageal cancer stem like cells. MTS assay showed that Sulforaphane decreased esophageal cancer growth, with an IC50 of 10 μmol/L for TE-13 and OE-33. At 5 μmol/L concentration, Sulforaphane eliminated the ALDH1A1-positive CSCs by 86% in the TE13 cell line, and by 68% in the OE33 cells. In conclusion, overexpression of ALDH1A1 in esophageal cancer cells is associated with poor prognosis. Meanwhile, Sulforaphane could be used to target ALDH1A1 positive cancer stem-like cells for cancer treatment.