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Peer-reviewedCC BY-NCJournal of gastric cancer

Biological Redefinition of Oligometastatic Gastric Cancer Refines Surgical Risk Stratification.

  • Yingying Wu1
  • Zhenxin Wang2
  • Min Fu1
  • Hong Zeng1
  • Yuan Gu1
  • Zhenbin Shen1
  • Kuntang Shen1
  • Yuehong Cui3
  • Tianshu Liu3
  • Yihong Sun4,5
  • Zhaoqing Tang1,6
  • Xuefei Wang1,7
7 affiliations
  1. 1Department of Gastrointestinal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  2. 2Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
  3. 3Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
  4. 4Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  5. 5Department of General Surgery, Zhongshan Hospital (Xiamen Branch), Fudan University, Xiamen, China. [email protected].
  6. 6Department of General Surgery, Zhongshan Hospital (Xiamen Branch), Fudan University, Xiamen, China. [email protected].
  7. 7Department of General Surgery, Zhongshan Hospital (Xiamen Branch), Fudan University, Xiamen, China. [email protected].
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Abstract

Purpose

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.Materials and methods

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.Results

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.Conclusions

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

Chinese Clinical Trial Registry: ChiCTR2500096665.

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Cite

BibTeXRIS
BibTeX
@article{wu2026biological,
  title = {{Biological Redefinition of Oligometastatic Gastric Cancer Refines Surgical Risk Stratification.}},
  author = {Yingying Wu and Zhenxin Wang and Min Fu and Hong Zeng and Yuan Gu and Zhenbin Shen and Kuntang Shen and Yuehong Cui and Tianshu Liu and Yihong Sun and Zhaoqing Tang and Xuefei Wang},
  journal = {Journal of gastric cancer},
  year = {2026},
  month = oct,
  doi = {10.5230/jgc.2026.26.e49},
  url = {https://europepmc.org/article/MED/42845260},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Biological Redefinition of Oligometastatic Gastric Cancer Refines Surgical Risk Stratification.
AU  - Yingying Wu
AU  - Zhenxin Wang
AU  - Min Fu
AU  - Hong Zeng
AU  - Yuan Gu
AU  - Zhenbin Shen
AU  - Kuntang Shen
AU  - Yuehong Cui
AU  - Tianshu Liu
AU  - Yihong Sun
AU  - Zhaoqing Tang
AU  - Xuefei Wang
PY  - 2026
DA  - 2026/10/01
JO  - Journal of gastric cancer
DO  - 10.5230/jgc.2026.26.e49
UR  - https://europepmc.org/article/MED/42845260
AB  - Purpose  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.Materials and methods  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.Results  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.Conclusions  The TIPscore provides a serum-based, biologically grounded framework for refining OMGC stratification and informing surgical decision-making.Trial registration  Chinese Clinical Trial Registry: ChiCTR2500096665.
SN  - 2093-582X
SN  - 2093-5641
ER  -