Decreased Expression of Retinoblastoma Protein-Interacting Zinc-Finger Gene 1 Is Correlated With Poor Survival and Aggressiveness of Cervical Cancer Patients.

Background: Retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) is a tumor suppressor deregulated in several human cancers. We aim to (1) explore RIZ1 expression in FIGO stages I-II cervical cancer tissues and its association with the clinical outcome of cervical cancer patients, (2) the role of RIZ1 in proliferation, apoptosis, migration, and invasion in cervical cancer cells. Methods: The expression of RIZ1 in 268 cervical cancer tissues and 30 paired adjacent non-tumor tissues were assessed by immunohistochemistry. We also examined RIZ1 at mRNA and protein level in 20 paired fresh frozen cervical cancer tissues and the adjacent non-tumor tissue using real-time PCR and western blot. We then examined proliferation, apoptosis, migration, and invasion in two human cervical cancer cells, HeLa and SiHa, with overexpression of RIZ1. Results: RIZ1 expression generally decreased in cervical cancer tissues. Decreased RIZ1 expression was significantly correlated with advanced FIGO stage (P = 0.005), deep stromal invasion (P = 0.001), lymphovascular space involvement (P = 0.041), pelvic lymph node metastasis (P = 0.005), and postoperative recurrence (P = 0.002). Kaplan-Meier analysis demonstrated that patients with low RIZ1 expression had shorter overall survival (OS) and disease-free survival (DFS) than those with high RIZ1 expression. Multivariate analysis showed that RIZ1 was an independent prognostic factor for DFS (HR = 2.184, 95% CI 1.365-3.496, P = 0.001) and OS (HR = 1.899, 95% CI 1.112-3.241, P = 0.019). In vitro analysis demonstrated that overexpression of RIZ1 inhibited cell proliferation, migration, and invasion, but promoted apoptosis in HeLa and SiHa cells. Conclusion: Down-regulation of RIZ1 may contribute to tumor migration, invasiveness, and poor survival of cervical cancer patients. RIZ1 may be a prognostic biomarker for cervical cancer patients.