Journal of Pathology and Translational Medicine

Original Articles

Increased Expression of Thymosin β4 Is Independently Correlated with Hypoxia Inducible Factor-1α (HIF-1α) and Worse Clinical Outcome in Human Colorectal Cancer: Seung Yun Lee, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Chang Nam Kim, Joo Heon Kim, Dong Wook Kang; J Pathol Transl Med. 2017;51(1):9-16. Published online October 16, 2016; DOI: https://doi.org/10.4132/jptm.2016.08.23

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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.

Citations

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Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis
Joanna I. Lachowicz, Giusi Pichiri, Marco Piludu, Sara Fais, Germano Orrù, Terenzio Congiu, Monica Piras, Gavino Faa, Daniela Fanni, Gabriele Dalla Torre, Xabier Lopez, Kousik Chandra, Kacper Szczepski, Lukasz Jaremko, Mitra Ghosh, Abdul-Hamid Emwas, Mass
International Journal of Molecular Sciences.2022; 23(1): 551. CrossRef
Metal coordination of thymosin β4: Chemistry and possible implications
Joanna Izabela Lachowicz, Mariusz Jaremko, Lukasz Jaremko, Giuseppina Pichiri, Pierpaolo Coni, Marco Piludu
Coordination Chemistry Reviews.2019; 396: 117. CrossRef
Adipose-Derived Mesenchymal Stem Cells Enhance Ovarian Cancer Growth and Metastasis by Increasing Thymosin Beta 4X-Linked Expression
Yijing Chu, Min You, Jingjing Zhang, Guoqiang Gao, Rendong Han, Wenqiang Luo, Tingting Liu, Jianxin Zuo, Fuling Wang
Stem Cells International.2019; 2019: 1. CrossRef
An Investigation on the Therapeutic Effect of Thymosinβ4 and Its Expression Levels in Streptozotocin-Induced Diabetic Mice
Kyung Sook Cho, Dong-Jin Kim, Bomee Shim, Jung Yeon Kim, Jun Mo Kang, Seon Hwa Park, Sang-Ho Lee, Hyung-In Yang, Kyoung Soo Kim
BioMed Research International.2018; 2018: 1. CrossRef
Hypoxia-inducible factor-1α expression in colorectal carcinoma
Ahmed M. Abd ElAziz, Hanan S. Abd ElHamid, Rasha R. Mostafa, Yousra R.A. Shalaby
Egyptian Journal of Pathology.2018; 38(1): 18. CrossRef

The Stromal Overexpression of Decay Accelerating Factor (DAF/CD55) Correlates with Poor Clinical Outcome in Colorectal Cancer Patients.: Tae Hwa Baek, Joo Heon Kim, Mee Ja Park, Hye Kyung Lee, Hyun Jin Son, Hyun Ki Soon, Chang Nam Kim, Che Myong Ko, Dong Wook Kang; Korean J Pathol. 2011;45(5):445-454.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.445

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Abstract PDF: 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.

Expression of Cyclin-Dependent Kinase-Associated Protein Phosphatase in Colorectal Carcinomas.: Chang Nam Kim, Soo Young Kim, Jae Wha Kim, Dong Wook Kang, Hyun Jin Son, Hye Kyung Lee, Mee Ja Park, Joo Heon Kim; Korean J Pathol. 2007;41(6):367-372.

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Abstract PDF: 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.

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