RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation.

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Advanced tumor molecular analysis risks heterogeneity and bias.
• Gastric cancer prognosis can be improved by analyzing early-stage tumors.
• Comparing RNA expression in early gastric cancers with and without lymph node metastasis is key.

Purpose of the Study:

• To develop a robust prognostic signature for gastric cancer.
• To identify molecular markers predicting poor prognosis in early gastric cancer.
• To validate the signature's predictive power in cell lines, animal models, and external patient cohorts.

Main Methods:

• Propensity score matching of 1003 early gastric cancers (Npos vs. Nneg).
• Machine learning and cross-validation to identify a 6-gene prognostic classifier.
• Functional validation in engineered cell lines, mouse models, and three external cohorts.

Main Results:

• A 6-gene signature (4 overexpressed, 2 downregulated) was identified.
• High-risk score correlated with increased invasion, migration, and chemoresistance.
• The risk score independently predicted overall and recurrence-free survival in external cohorts.

Conclusions:

• The 6-gene classifier-derived risk score reliably predicts gastric cancer prognosis.
• This signature offers a valuable tool for patient stratification and treatment decisions.