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基于血液蛋白质组学筛选非小细胞肺癌患者对安罗替尼的反应。

Screening anlotinib responders via blood-based proteomics in non-small cell lung cancer.

机构信息

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Shanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

FASEB J. 2022 Aug;36(8):e22465. doi: 10.1096/fj.202101658R.

Abstract

Anlotinib has been demonstrated to be effective in advanced non-small cell lung cancer (NSCLC) patients. The response stratification of anlotinib remains unclear. In this study, plasma samples from 28 anlotinib-treated NSCLC patients (discovery cohort: 14 responders and 14 non-responders) were subjected to proteomic analysis, and plasma samples from 35 anlotinib-treated NSCLC patients (validation cohort) were subjected to validation analysis. Liquid chromatography-tandem mass spectrometry analysis was performed on samples with different time points, namely baseline (BL), best response (BR), and progression disease (PD). Bioinformatics analysis was performed to screen for the underlying differential proteins. Enzyme-linked immunosorbent assay was performed to detect plasma ARHGDIB, FN1, CDH1, and KNG1 levels respectively. The Kaplan-Meier survival analysis was used for biomarker-based responsive stratification. Our results indicated that differential proteins between responders and non-responders showed that proteomic technology potentially contributes to biomarker screening in plasma samples at BL. Furthermore, our results suggested that the detection of plasma ARHGDIB, FN1, CDH1, and KNG1 levels have potential predictive value for anlotinib response both in the discovery cohort and validation cohort. Collectively, this study offers novel insights into the value of plasma biomarker screening via proteomic examination and suggests that plasma ARHGDIB, FN1, CDH1, and KNG1 levels could be used as biomarkers for anlotinib stratification in NSCLC patients.

摘要

安罗替尼已被证明对晚期非小细胞肺癌(NSCLC)患者有效。安罗替尼的反应分层仍不清楚。在这项研究中,对 28 名接受安罗替尼治疗的 NSCLC 患者(发现队列:14 名应答者和 14 名无应答者)的血浆样本进行了蛋白质组学分析,并对 35 名接受安罗替尼治疗的 NSCLC 患者(验证队列)的血浆样本进行了验证分析。对不同时间点的样本进行了液相色谱-串联质谱分析,即基线(BL)、最佳反应(BR)和进展疾病(PD)。生物信息学分析用于筛选潜在的差异蛋白。酶联免疫吸附试验(ELISA)分别检测血浆 ARHGDIB、FN1、CDH1 和 KNG1 水平。采用 Kaplan-Meier 生存分析进行基于生物标志物的应答分层。我们的研究结果表明,应答者和无应答者之间的差异蛋白表明蛋白质组学技术可能有助于 BL 血浆样本的生物标志物筛选。此外,我们的结果表明,在发现队列和验证队列中,检测血浆 ARHGDIB、FN1、CDH1 和 KNG1 水平对安罗替尼反应具有潜在的预测价值。总之,该研究通过蛋白质组学检查为血浆生物标志物筛选的价值提供了新的见解,并表明血浆 ARHGDIB、FN1、CDH1 和 KNG1 水平可作为 NSCLC 患者安罗替尼分层的生物标志物。

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