ABSTRACTThis study aimed to investigate the relationship between ZNF582promoter methylation (ZNF582m) level and radiosensitivity of cervical cancer and its biological basis. This was a prospective multicenter clinical study, comprising two independent cohorts of locally advanced cervical cancer patients. Exfoliated cervical cells were collected at 0, 24, 30, 36, 48, and 64 Gy to test ZNF582mlevels. Radiotherapy response was evaluated according to RECIST Version. RT-PCR and WT were used to detect the mRNA and protein expression levels; MTT and flow cytometry were used to detect the cell viability and cell cycle, respectively. While clone formation and subcutaneous tumorigenesis in nude mice were used to detect the growth of HeLa cells with/without ZNF582overexpression. In the first cohort, 22 cases achieved complete remission (CR) or partial response (PR), and the other 28 cases exhibited stable disease (SD). Radiotherapy reduced ZNF582mlevels among all patients. Initial lever of ZNF582mwas significantly higher in the Responder (CR + PR) group than in the SD group. Also, patients with higher initial lever ZNF582mwere more sensitive towards radiotherapy than ZNF582m-lowpatients. The second cohort confirmed the above results. The amplitude of ZNF582mlevels were related to the radiotherapeutic response; some patients of ZNF582m-lowshowed a transient increase in ZNF582m, and present greater radiosensitivity than other ZNF582m-lowpatients. In vitro, ZNF582 protein overexpression promoted cell cycle arrest in S phase. These results suggested that higher ZNF582mlevels predicted greater radiosensitivity in clinical cervical cancer cases. Overexpressed ZNF582 conferred radioresistance by cell cycle arrest in vitro.