Plasma immune proteome-based risk score predicts survival in advanced gastric cancer treated with PD-1 and chemotherapy

Zhouwei Zhan^1,2*Ruyu Lin^1,2Yigui Chen^1,2Sha Huang^1,2Luping Lin^1,2Hanchen Zheng^1,2Xiaojie Wang^1,2JW ZHENG^1,2Zengqing Guo^1,2Qiao Hu^1,2Bijuan Chen^1,2

• ¹Fujian Medical University, Fuzhou, China
• ²Fujian Provincial Cancer Hospital, Fuzhou, China

Background: Blood-based biomarkers that capture systemic immunity could complement tissue assays for prognostication in advanced gastric cancer receiving PD-1–based chemoimmunotherapy. We evaluated whether baseline plasma immune proteomics can stratify outcomes and be operationalized into a clinically usable model. Methods: In a prospective cohort (n=40) treated with first-line PD-1 inhibitor plus chemotherapy, nano-UHPLC–Orbitrap DIA-LC-MS/MS profiled baseline plasma. QC-filtered protein intensities were median-normalized, log2-transformed, and batch-adjusted as needed. Group structure was assessed by principal component analysis (PCA). Differential expression (two-sided testing; Benjamini–Hochberg FDR) and functional enrichment (GO/KEGG) were performed, with an immune focus defined using ImmPort sets. Prognostic screening used univariate Cox; features were reduced by LASSO-Cox and entered into multivariable models. A risk score (linear predictor of z-scaled abundances) was evaluated by Kaplan-Meier and time-dependent ROC. A nomogram integrating the proteomic score with clinical variables was calibrated by bootstrap. Results: 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 panel—LTB4R, 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 AUCs for OS at 6/12/18/24 months were 0.850/0.838/0.911/0.844, exceeding age, sex, grade, and PD-L1 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. Conclusions: Baseline plasma immune proteomics supports a compact, interpretable five-protein risk score that augments clinicopathologic variables for prognostic stratification under PD-1–based chemoimmunotherapy. The model is amenable to targeted assay translation and prospective validation for clinical deployment.