循环肿瘤DNA检测在去势抵抗型前列腺癌中的应用研究

Study of the Application of Circulating Tumor DNA Detection in Castration-Resistant Prostate Cancer

目的:研究循环肿瘤DNA检测在去势抵抗型前列腺癌(CRPC)中的临床价值。方法:选取广州医科大学附属第五医院2016年1月至2018年6月收治的56例前列腺癌患者为研究对象,将其分为CRPC组30例和非CRPC组26例。CRPC组于治疗前采用液体活检技术获得循环肿瘤DNA,非CRPC组于抗雄治疗前后采用液体活检技术获得循环肿瘤DNA,比较两组患者循环肿瘤DNA差异。结果:经液体活检,获具有临床检验应用前景的前列腺癌循环肿瘤DNA特异性标志基因:KLK2、KLK3、FOXA1和HOXB13。在KLK2、KLK3、FOXA1和HOXB13阳性表达率上,CRPC组均高于非CRPC组,差异具有统计学意义(P<0.05)。非CRPC组经12个月抗雄治疗后,12例患者诊断为CRPC。该12例患者在KLK2、KLK3、FOXA1和HOXB13阳性表达率上,抗雄治疗后均高于治疗前,差异具有统计学意义(P<0.05)。结论:经液体活检循环肿瘤DNA,CRPC患者本身存在KLK2、KLK3、FOXA1和HOXB13基因突变,且在去势治疗过程中同样发生上述特征的基因突变。

Objective To study the clinical value of circulating tumor DNA detection in castration-resistant prostate cancer(CRPC). Methods 56 patients with prostate cancer admitted to the fi fth affi liated hospital of Guangzhou medical university from January 2016 to June 2018 were divided into CRPC group(30 cases)and non-CRPC group(26 cases).Cyclic tumor DNA was obtained by liquid biopsy before treatment in CRPC group and by liquid biopsy before and after treatment in non-CRPC group.The difference of circulating tumor DNA between the two groups was compared. Results By liquid biopsy,DNA specific marker genes of circulating prostate cancer with clinical application prospect were obtained:KLK2,KLK3,FOXA1 and HOXB13.The positive expression rates of KLK2,KLK3,FOXA1 and HOXB13 in CRPC group were higher than those in non-CRPC group(P < 0.05).In the non-CRPC group,12 patients were diagnosed as CRPC after 12 months of antiandrogenic treatment.The positive expression rates of KLK2,KLK3,FOXA1 and HOXB13 in the 12 patients after anti-male treatment were higher than those before treatment,and the difference was statistically signifi cant(P < 0.05). Conclusion There are mutations in KLK2,KLK3,FOXA1 and HOXB13 genes in CRPC patients after liquid biopsy of circulating tumor DNA,and these mutations also occur during castration therapy.