TP53突变在中国前列腺癌患者中的临床特征及预后价值研究

Clinical features and prognostic value of TP53 mutation in Chinese prostate cancer patients

目的探讨中国前列腺癌患者循环肿瘤DNA(ctDNA)中TP53突变的临床特征及预后价值。方法前瞻性纳入2018年5月至2019年6月在复旦大学附属肿瘤医院泌尿外科确诊的239例前列腺癌患者,确诊年龄为(65.4±7.6)岁(范围:45~85岁)。通过目标序列捕获和二代测序检测血浆中ctDNA的TP53突变。分析接受不同治疗的患者TP53突变状态与无进展生存时间的相关性。对不同亚组进行Kaplan-Meier分析,绘制生存曲线,并采用Log-rank进行比较。采用Cox回归模型估算多变量校正后的HR及其与无进展生存时间相关的95%CI。结果存在TP53突变的患者比例为15.9%(38/239)。151例患者初诊时存在转移,TP53突变患者初诊转移比例更高[78.9%(30/38)比60.2%(121/201),χ^(2)=4.829,P=0.028],处于转移性去势抵抗阶段的比例更高[68.4%(26/38)比42.8%(86/201),χ^(2)=8.434,P=0.004]。TP53突变患者接受常规雄激素剥夺治疗、阿比特龙治疗、多西他赛治疗的中位无进展生存时间分别为13.0、4.7、3.0个月,TP53野生型患者分别为17.0、11.0、5.0个月。多因素分析结果显示,在接受阿比特龙治疗和多西他赛治疗的患者中,TP53突变是无进展生存时间的独立预后因素(HR=2.23,95%CI:1.26~3.94,P=0.006;HR=1.92,95%CI:1.01~3.66,P=0.047),在雄激素剥夺治疗患者中未发现这一趋势。结论TP53突变与存在转移、患者处于去势抵抗阶段相关,同时也是接受阿比特龙、多西他赛治疗患者的无进展生存时间的独立预后因素。

Objective To examine the clinical features and prognostic value of TP53 mutation in circulating tumor DNA(ctDNA)of Chinese prostate cancer patients.Methods A prospective cohort of 239 prostate cancer patients diagnosed in the Department of Urology,Fudan University Shanghai Cancer Center from May 2018 to June 2019 was included.The age of diagnosis was(65.4±7.6)years(range:45 to 85 years).Clinical data were collected from patient diagnosis and treatment records as well as follow-up surveys.TP53 mutations in plasma were detected by target sequence capture and second-generation sequencing.The relationship between TP53 mutation status and progression-free survival(PFS)was analyzed in patients who received any treatment lines.Kaplan-Meier analysis was performed in different subgroups,survival curves were drawn,and Log-rank test was used for comparison.Cox regression models were used to estimate multivariate adjusted HR and 95%CI associated with PFS.Results In the cohort,15.9%(38/239)patients had TP53 mutation.Patients with TP53 mutations had a higher rate of metastases initially diagnosed with prostate cancer(78.9%(30/38)vs.60.2%(121/201),χ^(2)=4.829,P=0.028),as well as a higher rate of castration resistance(68.4%(26/38)vs.42.8%(86/201),χ^(2)=8.434,P=0.004).Kaplan-Meier analysis revealed a median androgen-deprivation therapy-PFS of 13.0 months in patients with TP53 mutation and 17.0 months in patients with TP53 wild-type.The median abiraterone-PFS was 4.7 months for patients with TP53 mutation and 11.0 months for TP53 wild-type patients.The median docetaxel-PFS was 3.0 months in patients with TP53 mutation and 5.0 months in patients with TP53 wild-type.TP53 mutation was the undependent prognosis factor of PFS in patients treated with abiraterone(HR=2.23,95%CI:1.26 to 3.94,P=0.006)and docetaxel(HR=1.92,95%CI:1.01 to 3.66,P=0.047)had significant differences in PFS.Conclusions TP53 mutations were associated with the presence of metastasis and castration resistance,and were also an independent prognostic factor for progression-free survival in patients treated with abiraterone and docetaxel.