FOXM1 Promotes Tumor Cell Invasion and Predicts Poor Survival in Early-Stage Cervical Cancer
“High levels of FOXM1 expression were significantly associated with aggression in cervical cancer, and were an independent prognostic factor for poor survival in early-stage cervical cancer patients,” reported lead author Shan-yang He, MD, Department of Obstetrics and Gynecology, at the First Affiliated Hospital, Guangzhou, Peoples Republic of China, and coauthors.
The analysis of tumor cell profiles for 102 patients diagnosed with stage IA2-IIA2 cervical squamous-cell carcinoma; IA1-stage cases were excluded from analysis because they received only hysterectomy. FOXM1 expression was detected in tumor cells from 73.5% (75/102) of the patients. FOXM1 expression levels were associated with tumor growth (P=0.02), stromal invasion (P=0.02), and recurrence (P=0.01). Univariate and multivariate Cox regression analyses revealed that along with tumor size and parametrial tumor infiltration, FOXM1 expression is independently associated with patient survival (P<0.001).
“FOXM1 expression was significantly up-regulated at both mRNA and protein levels in early-stage cervical cancer, compared to cervical intraepithelial neoplasia and normal cervical tissues,” the authors wrote. “Moreover, enforced expression of FOXM1 increased migration and invasion of cancer cells, whereas RNAi-mediated knockdown of FOXM1 had the opposite effect.”
FOXM1 up-regulation triggered increased tumor cell expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, activated the Akt/glycogen synthase kinase-3β/Snail pathway, and resulted “in the promotion of migration and invasion of cervical cancer cells,” the team reported.
FOXM1 up-regulation's association with poor prognosis make it a promising prognostic biomarker for patients with early-stage cervical cancer and “a new potential target” for the treatment of cervical cancer, the team concluded.