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.
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BACKGROUND Decay accelerating factor (DAF/CD55), regulates the complement system by accelerating decay of the C3 convertase, has been described in several malignancies, however, the clinicopathologic significance of CD55 and its receptor CD97 has not been fully investigated. We examined the expression patterns of both CD55 and CD97 and their association with clinicopathologic parameters in colorectal cancers (CRCs). METHODS Expression patterns of CD55 and CD97 in the stroma and tumor cells at tumor center and invasive front were examined in 130 CRCs, and their significance was statistically evaluated. RESULTS CD55-high stroma was correlated with tumor border (p=0.006) and invasion depth (p=0.013). CD55-high tumor cells at tumor center and invasive front were correlated with histologic grade, and CD55-high tumor cells at invasive front with tumor, node and metastasis (TNM) stage (p<0.05).
CD97-high stroma was correlated with lymph node metastasis (p=0.016) and TNM stage (p=0.030). CD97-high tumor cells at tumor center and invasive front were correlated with tumor size and CD97-high tumor cells at tumor center with tumor border (p<0.05). Patients with CD55-high stroma showed poor overall and recurrence-free survival (p<0.05) in univariate analysis, and were independently associated with short recurrence-free survival (p=0.025) in multivariate analysis. CONCLUSIONS Stromal CD55 overexpression would be an indicator of adverse clinical outcome and a useful prognostic factor.
BACKGROUND Cyclin-dependent kinase-associated phosphatase (KAP) is a human dual-specificity protein phosphatase that dephosphorylates Cdk2 on threonine160 in a cyclin-dependent manner and that is known as an up-regulated molecule in some malignant tumors. We investigated the expression and clinicopathologic significance of KAP protein in relation to tumorigenesis of colorectal carcinoma. METHODS The expression patterns of KAP protein in tumor tissue were examined by reverse transcription-PCR and immunohistochemical staining. RESULTS An enhanced transcriptional level of KAP mRNA was observed in 11 out of 12 colorectal carcinoma specimens.
Immunohistochemical examination showed that KAP protein was more highly expressed in the tumors than that in the adjacent non-neoplastic mucosal tissues for 52 of 102 colorectal cancer tissues. The statistical analysis showed that an increased level of KAP protein in the colorectal cancer tissues was inversely correlated with the histologic grade, tumor size and Duke's stage. CONCLUSION The present study suggests that alteration of KAP might play a role, at least in part, in the tumorigenicity of colorectal carcinoma through the mechanism of cell cycle regulation.