A nomogram for predicting progression-free survival in stage III-IV gastric cancer based on post-treatment cholinesterase and C-reactive protein.

Authors

Dan Hu, Yumin Wang, Yongjie Zhang

Published in

Journal of gastrointestinal oncology. Volume 17. Issue 3. Pages 140. Jun 30, 2026. Epub May 14, 2026.

Abstract

Serum cholinesterase (CHE) and C-reactive protein (CRP) are established prognostic markers in gastric cancer, but their levels after two cycles of therapy are rarely incorporated into predictive models. This study aimed to develop a nomogram integrating post-treatment CHE and CRP levels after two cycles of first-line therapy to predict progression-free survival (PFS) in patients with stage III-IV gastric adenocarcinoma.
This retrospective study included 104 treatment-naïve patients with stage III-IV gastric adenocarcinoma who received first-line therapy. Serum CHE and CRP were measured after two cycles. Optimal prognostic cut-off values were determined by maximally selected rank statistics and validated via bootstrap resampling. Independent prognostic factors were identified by Cox regression to construct a nomogram. Model performance was evaluated using the concordance index (C-index), calibration plots, time-dependent receiver operating characteristic (ROC) analysis, and decision curve analysis (DCA). Overfitting was quantified by repeated K-fold cross-validation. Public transcriptomic data were analyzed via gene set variation analysis (GSVA) to explore associated pathways.
Optimal cut-off values were 4,865 U/L for CHE and 2.58 mg/L for CRP, confirmed by bootstrap validation. Multivariate analysis identified low post-treatment CHE (≤4,865 U/L) as an independent protective factor for PFS [hazard ratio (HR) =0.36; 95% confidence interval (CI): 0.20-0.63; P<0.001]. Elevated CRP (>2.58 mg/L) (HR =1.67; 95% CI: 0.99-2.84; P=0.06) and peritoneal metastasis (HR =1.66; 95% CI: 0.93-2.95; P=0.09) were associated with increased risk. The nomogram achieved a C-index of 0.709 (95% CI: 0.652-0.766), improving to 0.751 after cross-validation adjustment. Time-dependent ROC yielded areas under the curve (AUCs) of 0.789, 0.836, and 0.760 for 6-, 12-, and 18-month PFS, respectively. Risk stratification based on nomogram scores revealed significantly poorer PFS in the high-risk group (P<0.001). Bioinformatics analysis suggested upregulation of the complement and coagulation cascades pathway in advanced gastric cancer, correlating with poorer prognosis and M2-type macrophage infiltration.
A nomogram incorporating post-treatment CHE and CRP levels after two therapy cycles enables individualized PFS prediction and risk stratification in advanced gastric adenocarcinoma. The associated complement pathway may underlie an immunosuppressive tumor microenvironment.

PMID:
42434260
Bibliographic data and abstract were imported from PubMed on 11 Jul 2026.

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