外泌体has_circ_0000615预测曲妥珠单抗治疗转移性Her2(+)乳腺癌疗效的临床价值

Clinical Value of Exosome Has_circ_0000615 in Predicting the Efficacy of Trastuzumab in Metastatic Her2(+)Breast Cancer

目的分析血清外泌体环状RNA 0000615(has_circ_0000615)与转移性人表皮生长因子受体2阳性[Her2(+)]乳腺癌(BC)患者曲妥珠单抗治疗疗效的相关性。方法纳入我院2020年1月至2021年1月期间肿瘤科47例转移性Her2(+)BC女性患者,通过微阵列芯片分析活检组织标本中circRNAs差异性表达谱,并采用实时荧光定量PCR法检测血清外泌体has_circ_0000615表达水平。所有患者接受曲妥珠单抗一线治疗,每8周通过影像学检查进行一次疗效评价,将获得完全缓解(CR)和部分缓解(PR)的患者纳入敏感组,否则纳入耐药组。若CR+PR+疾病稳定(SD)≥6个月则视为临床获益。结果经微阵列芯片分析确定has_circ_0000615在Her2(+)BC组织中显著上调。所有患者中,敏感组患者血清外泌体has_circ_0000615表达水平逐渐降低(P<0.05),经受试者工作特征曲线分析,治疗前基线血清外泌体has_circ_0000615表达水平预测曲妥珠单抗一线治疗的临床获益的曲线下面积为0.666(95%CI 0.466~0.866)。基线血清外泌体has_circ_0000615高水平组患者骨转移发生率更高(P<0.05)。经Spearman相关性分析,0 d至30 d has_circ_0000615水平变化率与sHer2及癌胚抗原(CEA)水平变化率均呈显著正相关(r=0.584,0.291,P<0.05)。结论检测血清外泌体has_circ_0000615水平对于Her2(+)BC患者曲妥珠单抗的短期治疗结局能够提供一定的预测信息。

Objective To analyze correlation between serum exosomal circularRNA 0000615(has_circ_0000615)and trastuzumab treatment in patients with metastatic human epidermal growth factor receptor 2 positive[Her2(+)]breast cancer(BC).Methods From January 2020 to January 2021,47 female patients with metastatic Her2(+)BC in the Department of Oncology of our hospital were incorporated.The differential expression profile of circRNAs in biopsy tissue samples was analyzed by microarray chip,and the serum exosome has_circ_0000615 expression was detected by real-time quantitative PCR.All patients received trastuzumab first-line treatment and were evaluated by imaging every 8 weeks.Patients who achieved complete response(CR)and partial response(PR)were included in the sensitive group,otherwise they were included in the resistant group.CR+PR+stable disease(SD)≥6 months was considered as clinical benefit.Results Has_circ_0000615 was significantly upregulated in Her2(+)BC tissue by microarray analysis.In all patients,serum exosome has_circ_0000615 expression in sensitive group decreased gradually(P<0.05).Baseline serum exosome has_circ_0000615 expression before treatment predicted clinical benefit of trastuzumab first-line treatment with 0.666 area under the curve(95%CI 0.466~0.866).The incidence of bone metastasis was higher in patients with high baseline exosome has_circ_0000615 levels(P<0.05).Spearman correlation analysis showed that there was significant positive correlation between has_circ_0000615 and sHer2 and carcino-embryonic antigen(CEA)levels from 0 d to 30 d(r=0.584,0.291,P<0.05).Conclusion Detection of serum exosome has_cirC_0000615could provide predictive information for short-term treatment outcome of trastuzumab in Her2(+)BC patients.