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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-023-02790-x

摘要内容如下：

辅助化疗有益于切除的胰腺导管腺癌（PDAC）患者，但术后患者的身体状况可能会影响其依从性。需要生物标记物来识别快速辅助治疗的候选者。在这项前瞻性观察研究中，纳入了1171例接受胰腺切除术的PDAC患者，并进行了广泛的随访。191例患者样本的蛋白质组学分析揭示了临床相关的功能蛋白模块。为PDAC建立了蛋白质组学水平的预后风险模型，并使用公开的外部队列进一步验证了其实用性。更重要的是，通过利用临床和蛋白质组数据集的交互效应回归分析，我们发现了两个生物标记物（NDUFB8和CEMIP2），表明PDAC患者对辅助化疗的总体敏感性。在386名患者的内部队列中，通过免疫组织化学验证了生物标记物。严格的验证扩展到两个外部多中心队列-法国多中心队列（230例患者）和来自中国两个三级甲等医院的队列（466例患者）-增强了我们研究结果的稳健性和可推广性。此外，通过功能分析对PDAC细胞系和患者来源的类器官进行了实验验证。总之，我们的临床和蛋白质组数据的队列规模整合证明了蛋白质组学指导的预后和生物标志物辅助的PDAC辅助化疗的潜力。

英文原文如下：

Abstracts

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.

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