Prognostic Analysis Of TP53 K351N Mutati On-associated Platinum-resistance After Nact In Patient With Epithelial Ovarian Cancer

BACKGROUND: Treatment of epithelial ovarian carcinoma(EOC)involves neoadjuvant chemotherapy with interval debulking surgery(NACT-IDS)and primary debulking surgery(PDS)in two ways.A large number of studies have found that NACT-IDS has a significantly shorter progression-free survival(PFS)than PDS,and NACT-IDS has a higher recurrence probability than PDS within 6 months.The reason may be related to NACT-induced acquired platinum resistance.Its possible mechanism is related to the mutation of TP53 tetramerization domain(TP53 TD)and the loss of its anti-apoptotic function.PURPOSE: To study the status of TP53 TD mutation in PDS group and NACT group and its relationship with clinical prognosis in EOC patients,especially in NACT group.METHODS: The status of TP53 TD mutation was detected by tissue DNA extraction,nested PCR and DNA sequencing in 108 patients with EOC(including 51 patients in the NACT group and 57 patients in the PDS group).Clinical data were obtained by referring to cases and telephone follow-up and the correlation between TP53 TD mutation and platinum tolerance was analyzed.RESULTS: 1.In the 55 cases of ovarian cancer patients with neoadjuvant chemotherapy,there were 4 cases of ovarian cancer patients with TP53 K351 N mutation(7.8%,4/51)and appeared in 18 patients receiving 4-6 cycles of platinum-based NACT,the mutation probability was 22.2%(4/18).2.TP53 K351 N mutation was not detected in PDS group and the samples before neoadjuvant chemotherapy.3.There was a significant difference in overall survival curve and progression-free survival curve between the NACT group and the PDS group(POS = 0.013 PPFS = 0.005).The survival status of patients in the PDS group was significantly better than that in the NACT group.The probability of recurrence in the NACT group was 58.2%(30/51)within 6 months,which was significantly higher than that in the PDS group(35.1%,20/57).There was significant difference in recurrence rate between the two groups(P = 0.014).4.In the NACT group,the median PFS in patients with preoperative chemotherapy> 3 cycles was shorter than the median PFS in patients with preoperative chemotherapy ≤3 cycles,with a statistically significant difference(P = 0.044).Univariate and multivariate COX regression analysis showed that TP53 K351 N mutation was an independent factor in short PFS in patients with recurrence within 6 months of the NACT group(HR = 9.309,P = 0.043).Conclusions: 1)The treatment cycle > 3 cycles,platinum-based NACT may be one of the risk factors for TP53 K351 N mutation and drug resistance recurrence in ovarian cancer patients;2)The treatment cycle ≤ 3 cycles,platinum-based NACT may play a role in reducing the resistance of TP53K351N-mediated platinum-based drug resistance;3)Detection of TP53 K351 N mutation after NACT-IDS based on platinum is beneficial to avoid chemotherapy resistance and has important clinical significance in the selection of follow-up chemotherapy regimen.