The role of TMSB15A in gastric cancer progression and its prognostic significance.

Abstract

Background: Human thymosin β15 (TMSB15A) has been found to have protumorigenic effects in various malignant tumors, yet its function in gastric cancer (GC) remains unclear. This study investigated the value and function of TMSB15A in the diagnosis and tumorigenesis of GC, respectively.

Methods: Expression data for TMSB15A in GC tissues were analyzed using The Cancer Genome Atlas (TCGA). We evaluated the prognostic significance of TMSB15A through Kaplan-Meier survival analysis, time-dependent receiver operating characteristic (ROC) curves, and Cox regression models. Gene set enrichment analysis (GSEA) was performed to identify pathways associated with TMSB15A. In vitro assays assessed the effects of TMSB15A knockdown on GC cell proliferation, migration, and invasion.

Results: TMSB15A was significantly overexpressed in GC tissues compared to normal tissues (P<0.05). ROC analysis showed high diagnostic accuracy for TMSB15A (area under the curve =0.851, 95% confidence interval: 0.786-0.905, P<0.05). Kaplan-Meier survival analysis revealed that high TMSB15A expression was associated with poor overall survival, disease-specific survival, and progression-free survival. TMSB15A levels were correlated with advanced tumor stages (P<0.05), lymph node metastasis (P<0.01), and perineural invasion (P<0.05). GSEA showed significant enrichment of TMSB15A in inflammatory and oncogenic pathways, including interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), transforming growth factor β (TGF-β), and Hedgehog. Functional assays demonstrated that TMSB15A knockdown significantly reduced GC cell proliferation, migration, and invasion, suggesting that TMSB15A contributes to GC tumorigenesis and metastasis.

Conclusions: TMSB15A could serve as a prospective therapeutic target for GC due to its involvement in disease progression and metastasis.