外周血循环肿瘤细胞及人表皮生长因子受体2胞外区表达在进展期胃癌治疗疗效评估中的价值  

Value of serum human epithelial growth factor receptor 2 extracellular domain and circulating tumor cells in evaluating therapeutic response in advanced gastric cancer

作　　者：李一林[1] 彭智[1] 张小田[1] 龚继芳[1] 沈琳[1] 

机构地区：[1]北京大学肿瘤医院暨北京市肿瘤防治研究所消化肿瘤内科,恶性肿瘤发病机制及转化研究教育部重点实验室,100142

出　　处：《中华胃肠外科杂志》2017年第11期1293-1299,共7页Chinese Journal of Gastrointestinal Surgery

基　　金：国家重点研发计划资助（2017YFC1309000）;北京市自然科学基金重点项目（7161002）;首都卫生发展科研专项重点攻关项目（首发2016-1-1021）

摘　　要：目的研究人血清中表皮生长因子受体2胞外区（HER2 ECD）与外周血循环肿瘤细胞（CTC）的相关性，并进一步研究组织学HER2阴性或阳性胃癌患者中，HER2 ECD动态变化及与治疗疗效的关系。方法将北京大学肿瘤医院消化肿瘤内科2012年1月至2014年1月期间收治、并曾入组中国进展期胃癌CTC临床研究（ClinicalTrial gov. ID：NCT01625702）的53例患者入组本回顾性研究。入组条件：除病理组织学确诊为进展期胃癌外，至少接受2个周期以氟尿嘧啶为基础的化疗或联合靶向治疗，并同时进行了治疗前后外周血CTC的计数；按实体瘤的疗效评价标准（RECIST），治疗前至少具有一个可测量的靶病灶；患者需经医院伦理委员会同意及患者知情同意。留取患者治疗前及治疗2周期后的血清，利用化学发光免疫分析法进行血清样本中HER2 ECD水平的检测。HER2 ECD阳性阈值为≥15 ng/ml；CTC计数阳性阈值为≥3个/7.5 ml。采用Log-rank检验不同组间无进展生存期（PFS）及总体生存期（OS）的差异。结果53例进展期胃癌患者HER2阴性39例，HER2阳性的9例（17.0%），另5例检测状态未知。均接受氟尿嘧啶为基础的化疗，9例HER2阳性患者在化疗基础上联合抗HER2靶向治疗。治疗前全组血清HER2 ECD中位浓度为10.45（8.0-83.2）ng/ml；HER2 ECD阳性7例（13.2%），其中4例为HER2阳性患者外，3例HER2阴性患者同样存在血清HER2 ECD阳性；CTC中位数为2（0-668）个/7.5 ml，CTC阳性25例（47.2%）。HER2阴性患者中有10例治疗后血清HER2 ECD阳性，其中有2例患者在治疗前其HER2 ECD分别为83.3 ng/ml和46.9 ng/ml，治疗后则为22.4 ng/ml和20.4 ng/ml；另8例治疗前HER2 ECD均〈15 ng/ml（10.3-14.5 ng/ml），但在治疗2个周期后发生获得性HER2 ECD水平升高（15.1-19.5 ng/ml）。治疗后血清HER2 ECD水平升高患者外周血CTC水平通常较低，但相关性未达统计学差异。HER2阴性�Objective To examine the correlation between serum human epithelial growth factor receptor 2 extracellular domain （HER2 ECD） and circulating tumor cells （CTC）, as well as the dynamic variation of HER2 ECD and its correlation to the therapeutic efficacy. Methods Fifty-three advanced gastric cancer （AGC） patients who treated in Peking University Cancer Hospital and ever enrolled into CTC study （ClinicalTrial gov. ID： NCT01625702） were retrospectively included in this study. Inclusion criteria： the patients were histologically confirmed as locally advanced or recurrent and/ or metastatic adencarcinoma; they received two or more cycles of fluorouracil-based chemotherapy or combination targeted therapy; serum CTC was counted before and after therapy; the clinical response was evaluated every 2 cycles of treatment by the presence of at least one measurable lesion according to RECIST version 1.1 criteria. This study was approved by Ethics Committee of Peking University Cancer Hospital, and informed consents were signed by patients. The sera before and after two cycles of treatment were collected for CTC enumeration and HER2 ECD detection, in which the levels of HER2 ECD were measured by chemiluminescence immnnoassays method. The positive threshold value of HER2 ECD and CTC number were ≥ 15 μg/L and ≥3 CTCs/7.5 ml respectively. The progression-free survival （PFS） and overall survival （OS） were compared among different groups using Log-rank tests. Results In 53 enrolled patients, 39 were histologically identified as negative HER2, 9 as positive HER2 and another 5 cases were unknown. All the patients received fluorouracil-based chemotherapy, and 9 positive HER2 patients received combined anti-HER2 targeted therapy. Before therapy, the median HER2 ECD concentration of 53 cases was 10.45 （8.0 to 83.2） μg/L. Seven patients exhibited positive HER2 ECD levels, in whom 4 were histologically HER2 positive, but 3 were histologically HER2 negative. The median CTC number of 53 cases was 2 （0 t

关 键 词：胃肿瘤 进展期 液体活检 循环肿瘤细胞 人表皮生长因子受体2胞外区 疗效评估 

分 类 号：R735.2[医药卫生—肿瘤]