Janke Florian, Bozorgmehr Farastuk, Wrenger Sabine, Dietz Steffen, Heussel Claus P, Heussel Gudula, Silva Carlos F, Rheinheimer Stephan, Feisst Manuel, Thomas Michael, Golpon Heiko, Günther Andreas, Sültmann Holger, Muley Thomas, Janciauskiene Sabina, Meister Michael, Schneider Marc A
Division Cancer Genome Research, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany.
German Cancer Consortium (DKTK), INF 280, 69120 Heidelberg, Germany.
Cancers (Basel). 2020 Apr 12;12(4):954. doi: 10.3390/cancers12040954.
Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R = 0.78, R = 0.71, and R = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients' outcome.
计算机断层扫描（CT）是衡量非小细胞肺癌（NSCLC）治疗效果的金标准。在此，我们使用一组已确立的和探索性的液体生物标志物，研究了接受化疗或靶向治疗患者的极早期肿瘤反应。在基线期以及治疗开始后的三个早期时间点采集了50名患者的血样。对血清和血浆样本检测了DNA突变、一组17种微小RNA、糖蛋白1、谷胱甘肽二硫化物、谷胱甘肽、可溶性半胱天冬酶切割的细胞角蛋白18（M30抗原）以及可溶性细胞角蛋白18（M65抗原）。对基线期和首次随访的CT扫描进行了评估，并与生物标志物数据进行关联分析。各个生物标志物的检测率在56%至100%之间。虽然只有角蛋白18与基线期肿瘤负荷相关，但我们发现，在采血的三个时间点中的每个时间点，都有几种单独的标志物与肿瘤对治疗的反应相关。在每个时间点将五个最佳标志物组合起来，得到了高度显著的指示治疗反应的标志物组（R = 0.78、R = 0.71和R = 0.71）。我们的研究表明，在治疗开始后立即对生物标志物进行早期检测，可以评估肿瘤对治疗的反应，并可能有助于调整治疗方案以改善患者的预后。
