Biological Redefinition of Oligometastatic Gastric Cancer Refines Surgical Risk Stratification

The management of advanced gastric cancer (GC) follows a binary paradigm: surgery for localized disease versus palliative care for metastatic disease. Oligometastatic gastric cancer (OMGC) represents an intermediate state in which the role of surgery remains uncertain. Because current definitions of OMGC are based primarily on anatomic criteria and do not capture underlying biological heterogeneity, we developed the Tumor-Induced Perturbation score (TIPscore) to quantify systemic tumor-host perturbation and support biology-informed risk stratification.

Patients with advanced GC were stratified into locally advanced gastric cancer (LAGC), OMGC, and widely metastatic gastric cancer (WMGC) groups. Baseline serum samples from 107 patients were used to develop the TIPscore in the discovery cohort (LAGC=55, OMGC=22, WMGC=30), and post-treatment serum samples from 104 patients were used for longitudinal validation (LAGC=71, OMGC=30, WMGC=3). An independent temporal cohort of 147 patients with baseline serum samples was used for external validation (LAGC=105, OMGC=28, WMGC=14). Serum proteomic profiling was performed using the Olink platform, and the TIPscore was constructed by Elastic Net regression.

Three core proteins (IL-22RA1, HGF, and 4E-BP1) were incorporated into the TIPscore. The model positioned patients on a biological continuum of metastatic disease and showed consistent discriminatory performance across cohorts. The post-treatment TIPscore predicted 1-year overall survival in OMGC and may help stratify risk among patients with OMGC being considered for curative-intent surgery.

The TIPscore provides a serum-based, biologically grounded framework for refining OMGC stratification and informing surgical decision-making.

Chinese Clinical Trial Registry: ChiCTR2500096665.