Identification of plasma lipidomic biomarkers for prognostic stratification in advanced gastric cancer treated with PD-1 inhibitor plus chemotherapy

Cancer research · Gastric cancer

A plasma metabolite-based risk score derived from six biomarkers independently predicts survival in advanced GC treated with PD‑1‑based immunotherapy and offers a practical tool for individualized prognosis.

Background: Immunotherapy combined with chemotherapy has improved outcomes in advanced gastric cancer (GC), but reliable biomarkers to predict clinical benefit remain limited. Metabolomics provides a comprehensive assessment of systemic metabolic changes and may yield prognostic indicators to guide treatment selection. Methods: We performed untargeted liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) metabolomics on baseline plasma from 40 patients with advanced GC receiving first‑line programmed cell death protein‑1 (PD‑1) inhibitor plus chemotherapy. Patients were stratified into long‑term survivors (LTS) and short‑term survivors (STS) based on median overall survival (OS). Differential metabolites were identified using multivariate statistics, followed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis to construct a metabolite‑based risk score. Results: A total of 4,298 metabolites were detected, including 830 Level 1 and 1,321 Level 2 identifications. Six independent prognostic metabolites were identified. The resulting metabolite‑based risk score significantly stratified OS and progression‑free survival (p < 0.01) and demonstrated stable predictive accuracy over 6‑24 months. Compared with age, sex, tumor grade, and programmed death‑ligand 1 combined positive score (PD‑L1 CPS), the risk score showed superior discrimination. Conclusions: A plasma metabolite‑based risk score derived from six biomarkers independently predicts survival in advanced GC treated with PD‑1‑based immunotherapy and offers a practical tool for individualized prognosis.

The study demonstrates that a non‑invasive plasma lipidomic signature can prospectively identify patients with advanced gastric cancer who are more likely to benefit from first‑line PD‑1 inhibitor plus chemotherapy. This translates into an evidence‑based, personalized risk stratification tool that can inform clinical decision‑making and optimise patient outcomes.

Evidence level: Sejtvonalas. Laboratóriumi sejtekben vizsgálták.

Original source

Related signals