Cui Shiyun, Zheng Hejian, Xu Yiyang, Wu Qiuyu, Liu Weici, Cai Yucheng, Fan Lei, Tian Yitong, Qian Hao, Ding Yuting, Zhang Xinyi, Zhang Jiaguang, Wu Xiaofeng, Wang Rong, Li Xiangcheng, Chen Xiaofeng
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, P. R. China.
Department of oncology, Chongqing Hospital of Jiangsu Province Hospital (The People's Hospital of Qijiang District), Chongqing, 401420, China.
NPJ Precis Oncol. 2025 Apr 7;9(1):102. doi: 10.1038/s41698-025-00879-9.
Biliary tract cancer (BTC) has greatly influenced patient survival for years. Nowadays, immunotherapy represents a promising breakthrough and proteomics is one of powerful technologies in biomarker research. We collected plasma and tissue samples from 37 patients with advanced BTC and 92 proteins were analyzed by proximity extension assay (PEA). Through linear mixed effect models, compared to partial response (PR) group, 8 proteins, IL7, ANGPT2, IL15, HO-1, CXCL1, CXCL5, IL33, and VEGFA, exhibited significantly higher expression in stable disease and progressive disease (SD_PD) group in response-effect analysis. It was also revealed that a subset of proteins increased over time, including PDCD1, TNFRSF4, DCN, CRTAM, VEGFR-2 and ADA in PR group and PDCD1, IL10, ADA, CD28, and PTN in SD_PD group. In interaction-effect analysis, HO-1, ANGPT2, IL15 were three significant differentially expressed proteins (DEPs). Receiver operating characteristic (ROC) analysis further demonstrated that HO-1, ANGPT2, IL15 showed high accuracy in patients with immune checkpoint blockade (ICB) treatment plus chemotherapy (AUC = 0.74). In addition, based on the obtained plasma and tissue samples, two nomogram models were constructed for predicting the prognosis of BTC by genome combined with proteomics. Collectively meaningful proteomic biomarkers are beneficial to evaluate the efficacy of immunotherapy, and these discovered biomarkers may be included in the scope of treatments' evaluation and improvement in future study.
多年来，胆道癌（BTC）严重影响了患者的生存率。如今，免疫疗法是一个有前景的突破，而蛋白质组学是生物标志物研究中的强大技术之一。我们收集了37例晚期BTC患者的血浆和组织样本，并通过邻近延伸分析（PEA）对92种蛋白质进行了分析。通过线性混合效应模型，在反应 - 效应分析中，与部分缓解（PR）组相比，8种蛋白质，即IL7、ANGPT2、IL15、HO - 1、CXCL1、CXCL5、IL33和VEGFA，在疾病稳定和疾病进展（SD_PD）组中表现出显著更高的表达。还发现一部分蛋白质随时间增加，PR组中有PDCD1、TNFRSF4、DCN、CRTAM、VEGFR - 2和ADA，SD_PD组中有PDCD1、IL10、ADA、CD28和PTN。在交互作用分析中，HO - 1、ANGPT2、IL15是三种显著差异表达的蛋白质（DEPs）。受试者工作特征（ROC）分析进一步表明，HO - 1、ANGPT2、IL15在免疫检查点阻断（ICB）治疗加化疗的患者中具有较高的准确性（AUC = 0.74）。此外，基于获得的血浆和组织样本，构建了两个列线图模型，通过基因组学结合蛋白质组学来预测BTC的预后。总的来说，有意义的蛋白质组学生物标志物有助于评估免疫疗法的疗效，这些发现的生物标志物可能会在未来的研究中纳入治疗评估和改进的范围。
