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个体化生物标志物监测伊可替尼治疗晚期非小细胞肺癌患者的疾病进展。

Personalized biomarkers to monitor disease progression in advanced non-small-cell lung cancer patients treated with icotinib.

机构信息

Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.

Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.

出版信息

Clin Chim Acta. 2015 Feb 2;440:44-8. doi: 10.1016/j.cca.2014.11.010. Epub 2014 Nov 15.

Abstract

BACKGROUND

Disease-specific humoral immune response-related protein complexes in blood are associated with disease progression.

METHODS

Thirty-one patients with stage IIIB and IV non-small-cell lung cancer (NSCLC) were administered with oral dose of icotinib hydrochloride (150 mg twice daily or 125 mg 3 times daily) for a 28-continuous-day cycle until diseases progressed or unacceptable toxicity occurred. The levels of immunoinflammation-related protein complexes (IIRPCs) in a series of plasma samples from 31 NSCLC patients treated with icotinib hydrochloride were determined by an optimized native polyacrylamide gel electrophoresis.

RESULTS

Three characteristic patterns of the IIRPCs, named as patterns a, b, and c, respectively, were detected in plasma samples from 31 patients. Prior to the treatment, there were 18 patients in pattern a consisting of 5 IIRPCs, 9 in pattern b consisting of six IIRPCs, and 4 in pattern c without the IIRPCs. The levels of the IIRPCs in 27 patients were quantified. Our results indicate that the time length of humoral immune and inflammation response (TLHIIR) was closely associated with disease progression, and the median TLHIIR was 22.0 weeks, 95% confidence interval: 16.2 to 33.0 weeks, with a lead time of median 11 weeks relative to clinical imaging evidence confirmed by computed tomography or magnetic resonance imaging (the median progression-free survival, 34.0 weeks, 95% confidence interval: 27.9 to 49.0 weeks).

CONCLUSIONS

The complex relationships between humoral immune response, acquired resistance, and disease progression existed. Personalized IIRPCs could be indicators to monitor the disease progression.

摘要

背景

血液中与疾病特异性体液免疫反应相关的蛋白复合物与疾病进展有关。

方法

31 例 IIIB 期和 IV 期非小细胞肺癌(NSCLC)患者接受盐酸伊可替尼口服治疗(每日 2 次 150mg 或每日 3 次 125mg),28 天为一个连续周期,直至疾病进展或出现不可接受的毒性。通过优化的天然聚丙烯酰胺凝胶电泳测定 31 例接受盐酸伊可替尼治疗的 NSCLC 患者一系列血浆样本中的免疫炎症相关蛋白复合物(IIRPCs)水平。

结果

在 31 例患者的血浆样本中分别检测到三种特征性的 IIRPC 模式,分别命名为模式 a、b 和 c。在治疗前,模式 a 中有 18 例患者,包含 5 个 IIRPC;模式 b 中有 9 例患者,包含 6 个 IIRPC;模式 c 中有 4 例患者没有 IIRPC。对 27 例患者的 IIRPC 水平进行了定量分析。结果表明,体液免疫和炎症反应的时间长度(TLHIIR)与疾病进展密切相关,TLHIIR 的中位数为 22.0 周,95%置信区间为 16.2 至 33.0 周,与 CT 或 MRI 证实的临床影像学证据相比具有 11 周的领先时间(中位无进展生存期,34.0 周,95%置信区间:27.9 至 49.0 周)。

结论

体液免疫反应、获得性耐药与疾病进展之间存在复杂的关系。个性化的 IIRPC 可能是监测疾病进展的指标。

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