Dynamic alterations of site-specific N-glycoform and plasma proteasome signatures stratify chemotherapy benefit in pancreatic ductal adenocarcinoma.

Authors

Shanying Gui, Yaqiong Zhang, Tao Xia, Jiazi Qian, Zemin Fang, Wenhui Ouyang, Jie Wang, Jie Chen, Xiaojun Ren, Jianxin Lyu, Wei Cui, Hezhi Fang

Published in

Molecular & cellular proteomics : MCP. Pages 101642. Aug 17, 2026. Epub Aug 17, 2026.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) exhibits profound systemic remodeling during chemotherapy, yet how site-specific intact N-glycosylation in plasma is rewired by treatment remains largely undefined. Here, we perform an integrated plasma multi-omics study combining intact N-glycopeptidomics, deep proteomics, and metabolomics in a longitudinal cohort with paired pre- and post-chemotherapy samples and follow-ups (n = 177). Patients were further stratified according to radiographic treatment response. We identified 17,501 intact N-glycopeptides corresponding to 16,754 glycoforms, together with 6,045 proteins and 1,080 annotated metabolites. Paired analyses revealed extensive chemotherapy-associated changes across all three omics layers. Temporal glycopeptide and protein patterns were consistently enriched for complement, coagulation, extracellular-matrix, proteasome, and immune-related annotations, while oxidative-phosphorylation-related signatures showed relative depletion after treatment. Exploratory comparisons of within-patient changes (Δ = Post - Pre) between patients with partial response (PR) and those with stable or progressive disease highlighted 140 glycoforms, 18 glycosylation sites, and 103 proteins with response-associated patterns. These included coordinated increases in several proteasome-related plasma proteins in the PR group, as well as site- and glycoform-specific changes in complement- and acute-phase-related proteins. Response-associated differences in circulating metabolites further involved pyrimidine-, amino-acid-, and dipeptide-related features. Finally, leakage-controlled nested cross-validation prioritized 11 recurrent N-glycopeptide candidates and yielded modest prognostic discrimination, with a C-index of 0.591 and a 12-month area under the curve of 0.712. Collectively, this study provides a site- and glycoform-resolved view of chemotherapy-associated plasma molecular changes in PDAC and identifies candidate response- and prognosis-related features for future validation.

PMID:
42607870
Bibliographic data and abstract were imported from PubMed on 18 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.