Overexpression of DTL Relates to Tumor Cell Proliferation and Malignant Outcome of Esophageal Squamous Cell Carcinoma

Background Comparative genomic hybridization (CGH) method has contributed to the analysis of amplification and deletion of various genes. We detected Denticleless E3 ubiquitin protein ligase homolog (DTL) using the Agilent 244 k oligo-array CGH and FISH analyses for 1q32 amplification among 22 genes in esophageal squamous cell carcinoma (ESCC) and investigated DTL as a cancer promoting gene. Methods We analyzed 43 ESCC cell lines and 76 primary ESCC samples. Results 1) Overexpression of DTL mRNA was detected 100% (43/43) in ESCC cell lines compared to normal esophageal tissue. Knockdown of DTL expression drastically inhibited cell proliferation, induced G2/M arrest and inhibited migration and invasion. 2) Immunohistochemically, no expression was detected in normal esophageal tissue. Overexpression of DTL was detected in 25% (19/76) of ESCC tumors, and correlated with advanced N-stage. DTL positivity was an independent poor prognostic factor in multivariate analysis (P = 0.040, hazard ratio 2.4). Conclusion DTL plays a crucial role in malignant potential through overexpression, highlighting its utility as a prognostic factor, and a novel therapeutic target in ESCC.