TMEM119 and NRXN2 as prognostic biomarkers for liver metastasis in gastric cancer

Gastric cancer (GC) is a common digestive malignancy with high mortality, primarily due to liver metastasis. The underlying molecular mechanisms driving this process remain poorly understood. This study aimed to identify novel prognostic biomarkers for GC liver metastasis. We analyzed mRNA expression data from non-metastatic, liver-metastatic, and other-metastatic GC patient samples from The Cancer Genome Atlas (TCGA) database. Weighted gene co-expression network analysis (WGCNA) was employed to identify key gene modules and hub genes associated with liver metastasis. Potential biomarkers were screened based on differential expression, prognostic value determined by Kaplan-Meier survival analysis, and risk assessment via a univariate Cox regression model. The findings were then validated in an independent cohort of 380 GC patients. The WGCNA identified a gene module (MEgrey) significantly correlated with GC liver metastasis. Within this module, TMEM119 and NRXN2 were identified as key hub genes whose expression was significantly higher in the liver metastasis group compared to the non-metastatic and other-metastatic groups. High expression of either TMEM119 or NRXN2 was associated with shorter overall survival (OS) and indicated an increased risk of mortality (HR > 1). These findings were confirmed in our validation cohort. TMEM119 and NRXN2 are promising prognostic biomarkers for predicting liver metastasis in GC patients and may serve as potential therapeutic targets.