The nuclear protein expression levels of SNAI1 and ZEB1 are involved in the progression and lymph node metastasis of cervical cancer via the epithelial-mesenchymal transition pathway

摘要

Summary Growing evidence illustrates that aberrant activation of the epithelial-mesenchymal transition plays a key role in tumor cell invasion and metastasis. Transcription factors SNAI1 and ZEB1 regulate the epithelial-mesenchymal transition. To determine if SNAI1 and ZEB1 are involved in the metastasis of cervical cancer, we used immunohistochemistry to evaluate the expression of SNAI1, ZEB1, and vimentin in tumor and stromal compartments for a large set of cervical carcinoma samples. Results were evaluated using an H score (percentage × intensity). Of 70 samples, 64 cases (91.43%) were positive for SNAI1 expression. The median SNAI1 H score was 174.00 (range, 5-285). Sixty-seven cases (95.71%) were positive for ZEB1, with a median H score of 165.77 (range, 5-260). Nuclear expression of SNAI1 and ZEB1 in tumor cells was positively associated with International Federation of Gynecology and Obstetrics (FIGO) stages (P =.015 and P =.008, respectively) and lymph node metastasis (P =.007 and P =.007, respectively); meanwhile, expression of vimentin in tumor cells was positively associated with lymph node metastasis (P =.019). According to negative vimentin expression, nuclear expression of ZEB1 in tumor cells was positively associated with FIGO stages (P =.04). According to positive vimentin expression, nuclear expression of SNAI1 in tumor cells was positively associated with FIGO stages (P =.018) and pN (P =.029). In light of these findings, we propose that SNAI1 and ZEB1 have the potential to be used as a novel predictor of pelvic lymph node metastasis and represent promising therapeutic targets in patients with cervical cancer.