Feng Haokang, Chen Zhixue, Li Jianang, Feng Jiale, Yang Fei, Meng Fansheng, Yin Hanlin, Guo Yuquan, Xu Huaxiang, Liu Yuxin, Liu Runjie, Lou Wenhui, Liu Liang, Han Xu, Su Hua, Zhang Lei
Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
iScience. 2025 Jan 20;28(3):111693. doi: 10.1016/j.isci.2024.111693. eCollection 2025 Mar 21.
Pancreatic cancer (PC), characterized by the absence of effective biomarkers and therapies, remains highly fatal. Data regarding the correlations between PC risk and individual plasma proteome known for minimally invasive biomarkers are scarce. Here, we analyzed 1,345 human plasma proteins using proteome-wide association studies, identifying 78 proteins significantly associated with PC risk. Of these, four proteins (ROR1, FN1, APOA5, and ABO) showed the most substantial causal link to PC, confirmed through Mendelian randomization and colocalization analyses. Data from two clinical cohorts further demonstrated that FN1 and ABO were notably overexpressed in both blood and tumor samples from PC patients, compared to healthy controls or para-tumor tissues. Additionally, elevated FN1 and ABO levels correlated with shorter median survival in patients. Multiple drugs targeting FN1 or ROR1 are available or in clinical trials. These findings suggest that plasma protein FN1 associated with PC holds potential as both prognostic biomarkers and therapeutic targets.
胰腺癌（PC）因缺乏有效的生物标志物和治疗方法，致死率仍然很高。关于PC风险与以微创生物标志物闻名的个体血浆蛋白质组之间相关性的数据很少。在这里，我们使用全蛋白质组关联研究分析了1345种人类血浆蛋白，鉴定出78种与PC风险显著相关的蛋白质。其中，四种蛋白质（ROR1、FN1、APOA5和ABO）显示出与PC最显著的因果关系，通过孟德尔随机化和共定位分析得到证实。来自两个临床队列的数据进一步表明，与健康对照或癌旁组织相比，FN1和ABO在PC患者的血液和肿瘤样本中均显著过表达。此外，FN1和ABO水平升高与患者较短的中位生存期相关。有多种靶向FN1或ROR1的药物可供使用或正在进行临床试验。这些发现表明，与PC相关的血浆蛋白FN1有望作为预后生物标志物和治疗靶点。
