Elevated expression of iASPP correlates with poor prognosis and chemoresistance/radioresistance in FIGO Ib1-IIa squamous cell cervical cancer

Abstract

iASPP (inhibitory member of the ASPP family), the conserved key inhibitor of p53, is overexpressed and plays an important oncogenetic role in many human cancers. However, its function in cervical cancer remains unknown. The objective of this study was to investigate the expression and clinical relevance of iASPP in cervical cancer. The mRNA and protein expression levels of iASPP were determined by real-time quantitative reverse transcription with the polymerase chain reaction and Western blot. Paraffin sections of 149 patients with FIGO Ib1-IIa squamous cell cervical cancer were stained by using immunohistochemistry for iASPP, and its relationship with clinicopathologic parameters and prognosis of cervical cancer patients was analyzed. The mRNA and protein expression levels of iASPP were significantly elevated in cervical cancer tissues. The increased nuclear iASPP expression was correlated strongly with higher FIGO staging, deep cervical stromal invasion, pelvic lymph node metastasis, and poor overall and disease-free survival of patients with cervical cancer (all P<0.05). Multivariate Cox analysis showed that high nuclear iASPP expression was an independent prognostic factor for overall survival. Furthermore, patients with high nuclear iASPP expression were much more resistant to radiation or chemotherapy, resulting in poor overall and disease-free survival than those with low expression after receiving radiation or chemotherapy (all P<0.05) and indicating correlations with chemoresistance and radioresistance. This study thus demonstrates that iASPP is highly elevated in human cervical cancer, and that overexpression of nuclear iASPP is correlated with poor prognosis and chemoresistance/radioresistance, suggesting that iASPP might serve as a novel potential prognostic marker and therapeutic target for cervical cancer.