Elevated Expression of Inhibitor of Apoptosis-stimulating Protein of p53 (iASPP) and Methyltransferase-like 3 (METTL3) Correlate with Poor Prognosis in FIGO Ib1-IIa Squamous Cell Cervical Cancer

Background: Clinical outcomes of patients with early stage cervical cancer are determined by unique molecular events. Therefore, exploring novel biomarkers for the diagnosis and prognosis of cervical cancer is essential for guidance of cervical cancer treatment. Methods: Patients with FIGO Ib1-IIa cervical cancer who were treated with radical hysterectomy at the first affiliated hospital of Guangxi Medical University, China were included in the study. iASPP and METTL3 expression in the tumor specimens and adjacent non-tumor cervical tissues was determined by immunohistochemistry and western blot, and its relationship with clinicopathologic factors and prognosis of cervical cancer patients was analyzed. Results: Of 112 patients, 41 were stage Ib1, 22 Ib2, and 49 IIa. Their mean age was 45.3 years (range 25-75 years). Tumor size was 0.3 to 5.0 cm (mean 2.8 cm). Mean follow-up was 56.6 months (range 19-72 months). iASPP and METTL3 were higher in cervical cancer than normal cervix samples (p<0.001 and p<0.01, respectively). iASPP and METTL3 overexpression correlated with higher FIGO staging (p=0.013 and p=0.039, respectively), pelvic lymph node metastasis (p=0.002 and p=0.001, respectively), and poor 5-year recurrence-free survival, distant metastasis-free survival, progression-free survival, and overall survival rates (p=0.002, p=0.007, p=0.001, p=0.016, p=0.001, p<0.001, p=0.037, and p=0.042, respectively). High iASPP and METTL3 expression were independent prognostic factors (all p<0.05). The expression of iASPP was positively related with METTL3 (p=0.002). Conclusions: iASPP and METTL3 levels were elevated in cervical cancer, and they were both independent indicators for poor prognosis in early stage cervical cancer patients.