Yu Xie¹, Gang Fan², Chun Liu², Jian Lei², Mingji Ye², Zhengzhou Xu², Weiqing Han² 

¹Urology Department,Hunan Provincial Cancer Hospital, The affiliated Cancer Hospital of XiangyaMedical College, Central South University, ²The affiliated CancerHospital of Xiangya Medical College, Hunan Provincial Cancer Hospital

Objective:The standard treatment for patients withnon-muscle-invasive bladder cancer (NMIBC) is intravesical therapy followingtransurethral resection of bladder tumor (TURBT). However, only approximately10% to 40% of the patients can obtain disease-free survival for five years. Forhigh-risk patients, the disease progression rate for five years is raised to47%. Therefore, this study searches for an effective molecular predictivemarker for the identification of the instillation of chemotherapy sensitivityof patients with NMIBC. Transcription factor TFAP2α is a member of the AP-2family that can function as a tumor suppressor by regulating various genesinvolved in cell proliferation and apoptosis. Chemotherapeutic drugs, such ascisplatin, induce post-transcriptionally endogenous AP-2a, which contributes tochemosensitivity by enhancing therapy-induced apoptosis. Method: In thisstudy, the transcription factor AP-2a was selected from a previously identifiedfactor for predicting recurrence in NMIBC following the instillation ofchemotherapy. Immunohistochemistry assessed the AP-2a expression in 128 bladdertissues from patients with non-muscle-invasive bladder tumor. All patients werewithout any treatment before TURBT, although they underwent intravesicaltherapy after TURBT. To provide direct evidence for the role of AP-2a in NMIBC,the siRNA knockdown approach was used to suppress its expression in T24, Biu87.Result: Our study results showed that AP-2a was a strong independentpredictive marker for NMIBC patients treated with intravesical therapyfollowing TURBT. The patients with strong AP-2a staining had satisfactorydisease-free survival, whereas the patients with weak AP-2a staining hadhigh-risk of recurrence. Patients with the same levels of AP-2a protein couldobtain similar disease-free survival although they received different perfusiondrugs. In vitro studies demonstrate that bladder cell lines T24 and Biu87decreased sensitivity to pirarubicin and hydroxycamptothecin throughtransfection with siRNA targeting AP-2a transcript. Conclusion: Laboratorywork presented evidence that AP-2a may be involved in the regulation ofsensitivity of intravesical therapy in patients with pirarubicin andhydroxycamptothecin. AP-2a may have predicting recurrence potential for NMIBCpatients with chemotherapy.

Key Words: AP2a, Chemosensitivity,Bladder cancer