Associations of carboxypeptidase 4 with ALDH1A1 expression and their prognostic value in esophageal squamous cell carcinoma.

Abstract

Esophageal cancer is an aggressive disease with poor prognosis because of early metastasis when diagnosed and recurrence after surgery. This study is aimed at investigating the expression of carboxypeptidaseA4 (CPA4) and aldehyde dehydrogenase 1A1 (ALDH1A1) in esophageal squamous cell carcinoma (ESCC) tumor tissues and analyzed their association and clinical significance. The expression of CPA4 and ALDH1A1 was determined by immunohistochemistry using the corresponding primary antibodies on two commercial tissue arrays. High level of CPA4 was observed in 87/150 (58%) ESCC samples and was significantly associated with histologic grade, lymph node metastasis, and TNM Classification of Esophageal cancer stage. The expression level of ALDH1A1 was much higher in ESCC than their corresponding normal epithelial tissues, with 66% positive rate. And, high levels of ALDH1A1 were significantly associated with lymph nodes metastasis (P < 0.05) and TNM stage (P < 0.05). Correlation analysis showed the expression level of CPA4 positively correlated with that of ALDH1A1 (r = 0.416, P < 0.01). In Kaplan-Meier survival analysis, either CPA4 or ALDH1A1 was significantly correlated with poor overall survival of ESCC patients. Multivariate Cox regression model showed that high expression of CPA4 was an independent prognostic factor for ESCC patients. In conclusion, our present study demonstrated for the first time that CPA4 might be used as an independent poor prognostic factor in ESCC. This study demonstrated for the first time that CPA4 was aberrantly expressed in ESCC tissues. Overexpression of CPA4 was closely associated with the putative cancer stem cell marker ALDH1A1 and might be used as an independent prognostic factor in ESCC.