Label-free proteomics quantification of pancreatic ductal adenocarcinoma patient-derived xenografts with treatment combining Gemcitabine and nab-Paclitaxel

Tumor-stroma interactions are critical in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutics. Patient-derived xenograft (PDX) models faithfully recapitulate tumor-stroma interactions in PDAC, but conventional antibody-based immunoassay is largely inadequate to resolve or quantify tumor and stromal proteins. A species-deconvolved proteomics approach embedded in the ultra-high-resolution (UHR)-IonStar workflow can unambiguously quantify the proteins from tumor (human-derived) and stroma (mouse-derived) in PDX samples, enabling unbiased investigation of their proteomes with excellent quantitative reproducibility. With this strategy, 3 PDAC PDXs were analyzed. They were showed differential responses to treatment with Gemcitabine combined with nab-Paclitaxel (GEM+PTX), which is a first-line treatment regimen for PDAC. For each PDAC PDX, samples were collected after 24 hour and 192 hour with/without treatment, and each condition contained four biological replicates.

肿瘤-基质相互作用在胰腺导管腺癌（PDAC）的进展与治疗中具有关键意义。患者来源异种移植模型（PDX）可忠实复现PDAC的肿瘤-基质相互作用，但传统基于抗体的免疫测定法难以有效分辨或定量肿瘤与基质蛋白。嵌入超高分辨率（UHR）-IonStar工作流的物种解卷积蛋白质组学方法，能够对PDX样本中源自肿瘤的人类蛋白与源自基质的小鼠蛋白进行明确定量，从而实现对二者蛋白质组的无偏研究，并具备优异的定量重复性。本研究依托该策略分析了3株PDAC PDX模型，结果显示它们对吉西他滨联合纳米紫杉醇（GEM+PTX，PDAC一线治疗方案）的治疗应答存在差异。针对每株PDAC PDX，研究人员分别在给药与未给药条件下，于24小时和192小时采集样本，且每种条件均设置4个生物学重复。