{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T11:08:49Z","timestamp":1768216129767,"version":"3.49.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Blood-based biomarkers that capture systemic immunity could complement tissue-based assays for prognostication in advanced gastric cancer receiving programmed cell death protein 1 (PD-1)\u2013based chemoimmunotherapy. We evaluated whether baseline plasma immune proteomics can stratify clinical outcomes and be operationalized into a clinically usable model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a prospective cohort (n=40) treated with first-line PD-1 inhibitor plus chemotherapy, nano\u2013ultra-high-performance liquid chromatography (nano-UHPLC) coupled with Orbitrap data-independent acquisition liquid chromatography\u2013tandem mass spectrometry (DIA LC-MS\/MS) was used to profile baseline plasma. Quality control (QC)-filtered protein intensities were median-normalized, log\n                      <jats:sub>2<\/jats:sub>\n                      -transformed, and batch-adjusted as needed. Group structure was assessed by principal component analysis (PCA). Differential expression (two-sided testing; Benjamini-Hochberg false discovery rate [FDR] correction) and functional enrichment were performed, with an immune focus defined using Immunology Database and Analysis Portal (ImmPort) sets. Prognostic screening used univariate Cox proportional hazards regression; features were reduced by least absolute shrinkage and selection operator (LASSO)-Cox and entered into multivariable models. A risk score (linear predictor of z-scaled abundances) was evaluated by Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis. A prognostic nomogram integrating the proteomic score with clinical variables was calibrated by bootstrap resampling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PCA showed outcome-associated separation. Differential testing identified 322 proteins (179 up, 143 down in long-term survivors), including 36 immune-related differentially expressed proteins (DEPs). Penalized modeling selected a five-protein prognostic panel\u2014LTB4R, GBP2, HLA-G, CYBB, HLA-B. The risk score, dichotomized at the cohort median, stratified overall survival (OS) and progression-free survival (PFS) with clear separation. Time-dependent ROC area under the curve (AUC) values for OS at 6\/12\/18\/24 months were 0.850\/0.838\/0.911\/0.844, exceeding age, sex, grade, and programmed death-ligand 1 (PD-L1) combined positive score (CPS). In multivariable Cox models adjusting for clinical covariates, the score remained independently associated with OS. A nomogram combining the score with clinicopathologic factors yielded individualized 6-, 12-, and 18-month OS estimates with good calibration. Median PFS and OS for the overall cohort were 5.5 and 10.0 months, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Baseline plasma immune proteomics supports a compact, interpretable five-protein risk score that augments clinicopathologic variables for prognostic stratification under PD-1\u2013based chemoimmunotherapy. The model is amenable to targeted assay translation and prospective validation for clinical deployment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1715993","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:12:44Z","timestamp":1768205564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma immune proteome-based risk score predicts survival in advanced gastric cancer treated with PD-1 inhibitors and 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