Increased Expression of Thymosin β(4) Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer

BACKGROUND: Thymosin β(4) is a multi-functional hormone-like polypeptide, being involved in cell migration, angiogenesis, and tumor metastasis. This study was undertaken to clarify the clinicopathologic implications of thymosin β(4) expression in human colorectal cancers (CRCs). METHODS: We investigated tissue sections from 143 patients with CRC by immunohistochemistry. In addition, we evaluated the expression patterns and the clinico-pathological significance of thymosin β(4) expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series. RESULTS: High expression of thymosin β(4) was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β(4) showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β(4) and HIF-1α were overexpressed and that thymosin β(4) expression increased in parallel with HIF-1α expression in CRC. CONCLUSIONS: A high expression level of thymosin β(4) indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β(4) is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.