Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment

Abstract 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 pr...

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Main Authors: Shiyun Cui, Hejian Zheng, Yiyang Xu, Qiuyu Wu, Weici Liu, Yucheng Cai, Lei Fan, Yitong Tian, Hao Qian, Yuting Ding, Xinyi Zhang, Jiaguang Zhang, Xiaofeng Wu, Rong Wang, Xiangcheng Li, Xiaofeng Chen
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-025-00879-9
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author Shiyun Cui
Hejian Zheng
Yiyang Xu
Qiuyu Wu
Weici Liu
Yucheng Cai
Lei Fan
Yitong Tian
Hao Qian
Yuting Ding
Xinyi Zhang
Jiaguang Zhang
Xiaofeng Wu
Rong Wang
Xiangcheng Li
Xiaofeng Chen
author_facet Shiyun Cui
Hejian Zheng
Yiyang Xu
Qiuyu Wu
Weici Liu
Yucheng Cai
Lei Fan
Yitong Tian
Hao Qian
Yuting Ding
Xinyi Zhang
Jiaguang Zhang
Xiaofeng Wu
Rong Wang
Xiangcheng Li
Xiaofeng Chen
author_sort Shiyun Cui
collection DOAJ
description Abstract 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.
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spelling doaj-art-992bcc33e63f4cc2a9ea0cb8b2dab8a62025-08-20T02:11:59ZengNature Portfolionpj Precision Oncology2397-768X2025-04-019111210.1038/s41698-025-00879-9Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatmentShiyun Cui0Hejian Zheng1Yiyang Xu2Qiuyu Wu3Weici Liu4Yucheng Cai5Lei Fan6Yitong Tian7Hao Qian8Yuting Ding9Xinyi Zhang10Jiaguang Zhang11Xiaofeng Wu12Rong Wang13Xiangcheng Li14Xiaofeng Chen15Department of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of oncology, Chongqing Hospital of Jiangsu Province Hospital (The People’s Hospital of Qijiang District)Nanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityDepartment of General Surgery, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese MedicineNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityNanjing Medical UniversityHepatobiliar k77y Center, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityHepatobiliar k77y Center, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Oncology, The First Affiliated Hospital of Nanjing Medical UniversityAbstract 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.https://doi.org/10.1038/s41698-025-00879-9
spellingShingle Shiyun Cui
Hejian Zheng
Yiyang Xu
Qiuyu Wu
Weici Liu
Yucheng Cai
Lei Fan
Yitong Tian
Hao Qian
Yuting Ding
Xinyi Zhang
Jiaguang Zhang
Xiaofeng Wu
Rong Wang
Xiangcheng Li
Xiaofeng Chen
Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment
npj Precision Oncology
title Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment
title_full Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment
title_fullStr Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment
title_full_unstemmed Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment
title_short Plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving Camrelizumab plus the GEMOX treatment
title_sort plasma proteomic biomarkers predict therapeutic responses in advanced biliary tract cancer patients receiving camrelizumab plus the gemox treatment
url https://doi.org/10.1038/s41698-025-00879-9
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