Jia Bo, Zhao Xinghui, Wu Di, Dong Zhi, Chi Yujia, Zhao Jun, Wu Meina, An Tongtong, Wang Yuyan, Zhuo Minglei, Li Jianjie, Chen Xiaoling, Tian Guangming, Long Jieran, Yang Xue, Chen Hanxiao, Wang Jingjing, Zhai Xiaoyu, Li Sheng, Li Junfeng, Ma Menglei, He Yuling, Kong Lingdong, Brcic Luka, Fang Jian, Wang Ziping
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Medical Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Thoracic Oncology II, Peking University Cancer Hospital & Institute, Beijing, China.
Transl Lung Cancer Res. 2021 Feb;10(2):981-994. doi: 10.21037/tlcr-21-153.
Pemetrexed/platinum chemotherapy has been the standard chemotherapy regimen for lung adenocarcinoma patients, but the efficacy varies considerably.
To discover new serum biomarkers to predict the efficacy of pemetrexed/platinum chemotherapy, we analyzed 20 serum samples from advanced lung adenocarcinoma patients who received pemetrexed/platinum chemotherapy with the data-independent acquisition (DIA) quantitative mass spectrometry (MS).
The 20 patients were categorized as "good response" [12 patients achieving partial response (PR)] and "poor response" [8 patients with progressive disease (PD)] groups. Altogether 23 significantly different expressed proteins were identified, which had relative ratios higher than 1.2 or lower than -0.83, with 7 proteins having an area under the curve (AUC) above 0.8. To further validate the DIA results, we used the parallel reaction monitoring (PRM) method to examine 16 candidate serum biomarkers in the study cohort of 20 patients and another cohort of 22 advanced lung adenocarcinoma patients (16 PR and 6 PD). Quantitative validation using PRM correlated well with the DIA results, and 10 promising proteins exhibited a similar up- or downregulation. It is worth noting that glutathione peroxidase 3 (GPX3) exhibits significant upregulation in the poor response group compared with the good response group, which was validated by both DIA and PRM methods.
Our study confirmed that combined DIA MS and PRM approaches were effective in identifying serum predictive biomarkers for advanced lung adenocarcinoma patients. Further studies are needed to explore the potential biological mechanism underlying these biomarkers.
培美曲塞/铂类化疗一直是肺腺癌患者的标准化疗方案，但疗效差异很大。
为发现新的血清生物标志物以预测培美曲塞/铂类化疗的疗效，我们采用数据非依赖采集（DIA）定量质谱（MS）分析了20例接受培美曲塞/铂类化疗的晚期肺腺癌患者的血清样本。
20例患者被分为“良好反应”组（12例达到部分缓解[PR]）和“不良反应”组（8例疾病进展[PD]）。共鉴定出23种表达有显著差异的蛋白质，其相对比值高于1.2或低于-0.83，其中7种蛋白质的曲线下面积（AUC）大于0.8。为进一步验证DIA结果，我们采用平行反应监测（PRM）方法在20例患者的研究队列以及另一组22例晚期肺腺癌患者（16例PR和6例PD）中检测了16种候选血清生物标志物。使用PRM进行的定量验证与DIA结果相关性良好，10种有前景的蛋白质表现出相似的上调或下调。值得注意的是，与良好反应组相比，谷胱甘肽过氧化物酶3（GPX3）在不良反应组中显著上调，这通过DIA和PRM方法均得到了验证。
我们的研究证实，联合DIA MS和PRM方法可有效识别晚期肺腺癌患者的血清预测生物标志物。需要进一步研究以探索这些生物标志物潜在的生物学机制。
