J Pathol Transl Med.  2017 Jan;51(1):9-16. 10.4132/jptm.2016.08.23.

Increased Expression of Thymosin β₄ Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer

• Lee SY
• Park MJ
• Lee HK
• Son HJ
• Kim CN
• Kim JH
• Kang DW

• KMID: 2367675
• DOI: http://doi.org/10.4132/jptm.2016.08.23

Abstract

BACKGROUND
Thymosin β₄ 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 β₄ 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 β₄ expression in association with hypoxia inducible factor-1α (HIF-1α) expression in the CRC series.
RESULTS
High expression of thymosin β₄ was significantly correlated with lymphovascular invasion, invasion depth, regional lymph node metastasis, distant metastasis, and TNM stage. Patients with high expression of thymosin β₄ showed poor recurrence-free survival (p = .001) and poor overall survival (p = .005) on multivariate analysis. We also found that thymosin β4 and HIF-1α were overexpressed and that thymosin β₄ expression increased in parallel with HIF-1α expression in CRC.
CONCLUSIONS
A high expression level of thymosin β₄ indicates poor clinical outcomes and may be a useful prognostic factor in CRC. Thymosin β₄ is functionally related with HIF-1α and may be a potentially valuable biomarker and possible therapeutic target for CRC.

Keyword

Thymosin β₄; Hypoxia inducible factor-1α; Hypoxia; Immunohistochemistry; Colorectal cancer

MeSH Terms

Anoxia*
Cell Movement
Colorectal Neoplasms*
Humans*
Immunohistochemistry
Lymph Nodes
Multivariate Analysis
Neoplasm Metastasis
Thymosin*
Thymosin

Figure

• 

  Fig. 1. Immunohistochemical expression of thymosin β4 (A–D) and hypoxia inducible factor-1α (HIF-1α) (E–H) in human colorectal cancer. (A) No or weak expression of thymosin β4 in normal colonic epithelium. (B) Low expression of thymosin β4 in tumor glands. (C) Tumor cells show high thymosin β4 expression, but no or weak thymosin β4 expression in normal colonic epithelium. (D) Tumor cells reveal strong thymosin β4 expression primarily in the cytoplasm of tumor cells. (E) No or weak immunoreactivity of HIF-1α in normal colonic epithelium. (F) Low expression of HIF- 1α in tumor cells. (G) Tumor cells show strong HIF-1α expression. (H) HIF-1α is highly expressed predominantly in the nucleus of tumor cells.

• 

  Fig. 2. Kaplan-Meier survival analysis by thymosin β4 expression status. (A) Cumulative recurrence-free survival differences between patients with high and low thymosin β4 expression. (B) Cumulative overall survival differences between patients with high and low thymosin β4 expression. p-values were obtained using the log-rank test of differences.

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