Galectin-7 as a biomarker for aggressiveness and poor prognosis in thymic epithelial tumors.

OBJECTIVE: To identify molecular determinants of tumor aggressiveness in TETs and to elucidate their functional roles and underlying mechanisms in tumor progression. METHODS: We performed proteomic profiling using data-independent acquisition mass spectrometry on 40 TET samples and their paired adjacent normal tissues to explore potential molecular differences. TETs were stratified into high-risk (WHO types B2, B3, and thymic carcinoma) and low-risk (types A, AB, and B1) groups based on histological classification. Gene set enrichment analysis (GSEA) was applied to the proteomic data to delineate pathways enriched in high-risk tumors. A validation cohort comprising 164 TET patients, along with 6 non-TET controls, was analyzed to assess Galectin-7 expression by immunohistochemistry and to evaluate its prognostic value. To further explore the biological role of Galectin-7, functional assays were performed in Tc1889 cells following Galectin-7 overexpression. RESULTS: Proteomic analysis revealed Galectin-7 as a highly upregulated protein in high-risk TETs. GSEA analysis identified enrichment of mitochondrial and extracellular matrix-related pathways in high-risk tumors. Immunohistochemistry showed Galectin-7 expression in 82 % of high-risk TETs and only 13 % of low-risk TETs (p < 0.001), with higher expression correlating with advanced tumor stage and reduced progression-free survival. Functional assays demonstrated that Tc1889 cells with Galectin-7 overexpression exhibited enhanced proliferation and invasion. Additionally, MAPK signaling pathway activation was observed in Galectin-7-overexpressing cells. CONCLUSIONS: Galectin-7 is a potential biomarker for aggressive TETs, with expression levels associated with features of poor prognosis. These findings provide insight into TET biology and support further exploration of Galectin-7 in tumor stratification and therapeutic research.