Tenascin-C as a potential biomarker and therapeutic target for esophageal squamous cell carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Esophageal squamous cell carcinoma (ESCC) poses a significant health challenge.
• Tenascin-C (TNC) is implicated in tumor progression but its prognostic and therapeutic roles in ESCC require further elucidation.

Purpose of the Study:

• To develop a prognostic model for ESCC patients using TNC expression and clinicopathological features.
• To investigate the therapeutic implications of inhibiting TNC in ESCC.

Main Methods:

• Immunohistochemistry (IHC) to quantify TNC expression in ESCC tissues.
• Cox regression and nomogram construction for prognostic modeling.
• In vitro and in vivo studies assessing TNC knockdown effects.
• RNA-sequencing and GSEA to identify TNC-regulated pathways.
• Evaluation of combination therapy with TNC inhibition and small-molecule inhibitors.

Main Results:

• TNC was significantly overexpressed in ESCC tissues compared to normal tissues (48.77% vs 2%).
• A nomogram integrating TNC expression, pT stage, and lymph node metastasis demonstrated strong prognostic performance.
• TNC knockdown suppressed ESCC cell proliferation and xenograft growth, downregulating key tumor growth pathways.
• TNC inhibition potentiated the efficacy of inhibitors targeting EGFR, PI3K-Akt, Ras, and MAPK pathways.

Conclusions:

• The developed nomogram serves as a promising tool for ESCC survival prediction.
• Reducing TNC expression enhances ESCC cell sensitivity to EGFR and downstream pathway inhibitors, suggesting a novel combination therapy strategy.