State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institutes of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
Nat Commun. 2024 Feb 1;15(1):980. doi: 10.1038/s41467-024-44911-1.
Cetuximab therapy is the major treatment for colorectal cancer (CRC), but drug resistance limits its effectiveness. Here, we perform longitudinal and deep proteomic profiling of 641 plasma samples originated from 147 CRC patients (CRCs) undergoing cetuximab therapy with multi-course treatment, and 90 healthy controls (HCs). COL12A1, THBS2, S100A8, and S100A9 are screened as potential proteins to distinguish CRCs from HCs both in plasma and tissue validation cohorts. We identify the potential biomarkers (RRAS2, MMP8, FBLN1, RPTOR, and IMPDH2) for the initial response prediction. In a longitudinal setting, we identify two clusters with distinct fluctuations and construct the model with high accuracy to predict the longitudinal response, further validated in the independent cohort. This study reveals the heterogeneity of different biomarkers for tumor diagnosis, the initial and longitudinal response prediction respectively in the first course and multi-course cetuximab treatment, may ultimately be useful in monitoring and intervention strategies for CRC.
西妥昔单抗治疗是结直肠癌（CRC）的主要治疗方法，但药物耐药性限制了其疗效。在这里，我们对 147 例接受西妥昔单抗多疗程治疗的 CRC 患者（CRC）的 641 份血浆样本进行了纵向和深度蛋白质组学分析，并对 90 名健康对照（HC）进行了分析。在血浆和组织验证队列中，COL12A1、THBS2、S100A8 和 S100A9 被筛选为潜在蛋白，以区分 CRC 和 HCs。我们确定了潜在的生物标志物（RRAS2、MMP8、FBLN1、RPTOR 和 IMPDH2），用于预测初始反应。在纵向研究中，我们发现了两个具有不同波动的簇，并构建了一个具有高精度的模型来预测纵向反应，该模型在独立队列中得到了进一步验证。这项研究揭示了不同生物标志物在肿瘤诊断、初始和纵向反应预测方面的异质性，分别在西妥昔单抗治疗的第一疗程和多疗程中，最终可能对 CRC 的监测和干预策略有用。
