Elucidating the Role of THPO and Related Molecular Markers in Lymph Node Metastasis and Prognosis of Gastric Cancer: Insights From TCGA Data Analysis

<b>Background:</b> Gastric cancer poses a substantial public health burden, with rising mortality rates in metastatic stages. Elucidating the molecular mechanisms underlying lymph node metastasis is critical for developing novel therapeutic interventions. <b>Methods:</b> Using data from the Cancer Genome Atlas (TCGA), we stratified gastric cancer patients by lymph node metastasis stage (N0-N3) to identify key molecular determinants of metastatic progression. Integrated bioinformatic analyses included differential gene expression profiling, protein-protein interaction networks, survival analysis, and immune microenvironment characterization, with a focused investigation of THPO. <b>Results:</b> We identified metastasis-associated genes, notably THPO, which exhibited stage-dependent upregulation in advanced lymph node metastasis (N3). Elevated THPO expression correlated significantly with adverse prognostic outcomes, including reduced overall survival, disease-free survival, and progression-free survival (all <i>p</i> < 0.05). Mechanistically, THPO promoted epithelial-mesenchymal transition and showed a positive correlation with M2 macrophage infiltration, implicating it in tumor progression. Furthermore, a THPO-centric prognostic signature demonstrated high accuracy in predicting 1-, 3-, and 5-year survival rates (AUC > 0.80), supporting its clinical utility. Furthermore, THPO knockdown in MKN-45 cells suppressed migration and blunted the EMT pathway, confirming its prometastatic role in gastric cancer. <b>Conclusion:</b> Our findings establish THPO as a promising biomarker and therapeutic target in gastric cancer. Molecular insights into lymph node metastasis may facilitate the development of precision prognostic tools and tailored therapeutic strategies, highlighting the imperative for further mechanistic and translational studies.