Longitudinal plasma proteomic analysis identifies biomarkers and combinational targets for anti-PD1-resistant cancer patients

• DOI: 10.1007/s00262-024-03631-7
• Publication Date: 2024-02-13T12:02:29Z
• Authors: Qiaoyun Tan; Ruyun Gao; Xiaomei Zhang; Jianliang Yang; Puyuan Xing; Sheng Yang; Dan Wang; Guibing Wang; Shasha Wang; Jiarui Yao; Zhishang Zhang; Le Tang; Xiaobo Yu; Xiaohong Han; Yuankai Shi
• Keywords: Proteome

Abstract The response rate of anti-PD1 therapy is limited, and the influence on cancer patients unclear. To address these challenges, we conducted a longitudinal analysis plasma proteomic changes with in non-small cell lung (NSCLC), alveolar soft part sarcoma (ASPS), lymphoma patients. We included 339 samples before after from 193 NSCLC, ASPS, or lymphoma. proteins were detected using data-independent acquisition-mass spectrometry customable antibody microarrays. Differential characteristics responders (R) non-responders (NR) elucidated. A total 1019 our in-depth proteomics platform distributed across 10–12 orders abundance. By comparing differential proteome expression between R NR groups, 50, 206, 268 identified patients, respectively. Th17, IL-17, JAK-STAT signal pathways upregulated group, while cellular senescence transcriptional misregulation activated group. Longitudinal revealed IL-17 signaling pathway was downregulated treatment. Consistently, many as potential combinatorial therapeutic targets (e.g., IL-17A CD22). Five noninvasive biomarkers (FLT4, SFTPB, GNPTG, F5, IL-17A) further validated an independent cohort ( n = 39), another three (KIT, CCL3, TNFSF1) NSCLC 76). Our results provide molecular insights into identify new strategies for anti-PD1-resistant