晚期NSCLC患者EGFR-TKI治疗过程中血清多肽变化及其临床意义的探索性研究

背景与目的本研究旨在应用基质辅助激光解析离子化-时间飞行质谱仪（matrix-assisted laser desorption ionization time-of-lfight mass spectrometry, MALDI-TOF-MS）检测晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）患者在接受表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factorreceptor tyrosine kinase inhibitors, EGFR-TKIs）治疗过程中血清多肽的变化并探索其临床意义。方法收集34例接受EGFR-TKI治疗的晚期NSCLC患者TKI治疗前、最佳疗效时及疾病进展后的自身配对血清样本102份。处理血清样本并应用MALDI-TOF-MS检测，得到质谱图后使用CPT统计软件进行分析，鉴定出差异多肽，并对其临床意义进行分析。结果34例接受EGFR-TKI治疗的患者无完全缓解（complete response, CR）患者，部分缓解（partial response, PR）11例，疾病稳定（stable disease, SD）23例，中位无进展生存期（progression-free survival, PFS）为8.0个月（95%CI：6.6-11.2）；中位总生存期（overall survival, OS）为11.4个月（95%CI：10.6-16.5）。对TKI治疗的三个不同时间点的血清进行质谱检测，结果显示三个时间点多肽指纹图谱均不相同；配对分析最佳疗效时与基线时质谱数据经CPT软件共鉴定出差异多肽峰87个，筛选出两组间有统计学差异[P<0.001、曲线下面积（area under curve, AUC）≥0.9]的多肽峰1个；疾病进展时与基线时共鉴定出差异多肽峰96个，筛选出两组间有统计学差异（P<0.001, AUC≥0.9）的多肽峰3个；最佳疗效时与疾病进展时共鉴定出差异多肽峰115个，筛选出两组间有统计学差异（P<0.001, AUC≥0.9）的多肽峰4个。结论 NSCLC患者TKI治疗过程中血清多肽存在动态变化，差异多肽可能与治疗效果、疾病进展相关，差异多肽的特性、临床意义需进一步鉴定和验证。

Preliminary Study of Differentially Expressed Serum Peptides of Advanced NSCLC Patients Responsive to EGFR-TKI and Their Clinical Signiifcance

Background and objectivehTis study aimed at using matrix-assisted laser desorption ionization - time of lfight mass spectrometer (matrix-assisted laser desorption ionization time-of-lfight mass spectrometry, MALDI-TOF-MS) screening the difference serum peptides during epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment and exploring their signiifcance of advanced NSCLC patients.MethodsCollect 102 serum samples from 34 advanced NSCLC pa-tients, which are before TKI treatment, best effect of treatment and atfer progession. Peptides were extracted from the samples and then detected by MALDI-TOF-MS system to get the mass spectra. hTe mass spectra data was analyzed by the Clinpro-ToolTM sotfware to identify the different serum peptides, and then analyzed the clinical signiifcance of peptides.Results Among the 34 patients who received TKI treatment, there were none evaluated as complete response (CR), 11 patients evalu-ated as PR and 23 patients evaluated as stable disease (SD), with the PFS was 8.0 months (95%CI: 6.6-11.2); overall survival (OS) was 11.4 months (95%CI: 10.6-16.5). Atfer detected the serum from three different points of time, the result showed that they were totally different; 87 different peptide peaks were identiifed atfer analysis self-paired serum between the time of best effect and baseline, which included one statistically different [P<0.001, area under curve (AUC)≥0.9] peptide; 96 different peptide peaks were identiifed atfer analysis serum between the time of progression and baseline, which included 3 statistically different (P<0.001, AUC≥0.9) peptides; 115 different peptide peaks were identiifed atfer analysis serum between the time of progression and best effect, which included 4 statistically different (P<0.001, AUC≥0.9) peptides.ConclusionhTeserum peptides of NSCLC patients in the process of TKI treatment are dynamic and the different peptides may be associated with treatment effect and disease progression. However, the features and clinical signiifcance of different peptides need to be vali-dated in the future.