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.

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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

Clinicopathologic Implications of PIWIL2 Expression in Colorectal Cancer: Sun-Ju Oh, Su-Mi Kim, Young-Ok Kim, Hee-Kyung Chang; Korean J Pathol. 2012;46(4):318-323. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.318

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Abstract PDF

Background

There are no established reports about the expression of the Piwil gene, a subfamily of the Piwi gene involved in RNA silencing and self-renewal, in colorectal carcinomas. It is known that the degree of PIWIL2 expression is higher in colorectal carcinomas. But its clinicopathologic significance remains undetermined. This study reassessed the relationship between PIWIL2 expression and the clinicopathologic parameters in colorectal carcinomas.

Methods

An immunohistochemistry of PIWIL2 expression was done in 60 cases of colorectal carcinoma. This was followed by an analysis of the correlation between PIWIL2 expression and clinicopathologic features and a survival analysis.

Results

There were 44 cases (73.3%) where the degree of PIWIL2 expression was relatively higher. The high degree of PIWIL2 expression was significantly correlated with the lower degree of differentiation (p=0.039), deep invasion (p=0.019) and perineural invasion (p=0.027). The overall survival was longer in patients with the lower degree of PIWIL2 expression than in those with the higher degree of PIWIL2 expression.

Conclusions

Our results showed that the degree of PIWIL2 expression was relatively higher in colorectal carcinomas and it was significantly correlated with variable clinicopathologic indicators for a poor prognosis. This indicates that PIWIL2-positive cells contribute to the progression of colorectal cancer.

Citations

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Critical appraisal of the piRNA-PIWI axis in cancer and cancer stem cells
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Piwi-interacting RNAs (piRNAs) and Colorectal Carcinoma: Emerging Non-invasive diagnostic Biomarkers with Potential Therapeutic Target Based Clinical Implications
Suman Kumar Ray, Sukhes Mukherjee
Current Molecular Medicine.2023; 23(4): 300. CrossRef
piRNA: A promising biomarker in early detection of gastrointestinal cancer
Melika Ameli Mojarad, Mandana Ameli Mojarad, Bahador Shojaee, Ehsan Nazemalhosseini-Mojarad
Pathology - Research and Practice.2022; 230: 153757. CrossRef
The function of novel small non‐coding RNAs (piRNAs, tRFs) and PIWI protein in colorectal cancer
Mandana AmeliMojarad, Melika AmeliMojarad, Jian Wang
Cancer Treatment and Research Communications.2022; 31: 100542. CrossRef
Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response
Ailec Ho-Plágaro, Cristina Rodríguez-Díaz, Concepción Santiago-Fernández, Carlos López-Gómez, Sara García-Serrano, Flores Martín-Reyes, Francisca Rodríguez-Pacheco, Alberto Rodríguez-Cañete, Guillermo Alcaín-Martínez, Luis Vázquez-Pedreño, Sergio Valdés,
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Emerging roles of PIWI-interacting RNAs (piRNAs) and PIWI proteins in head and neck cancer and their potential clinical implications
Trisha Chattopadhyay, Priyajit Biswal, Anthony Lalruatfela, Bibekanand Mallick
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Cytokine-mediated crosstalk between cancer stem cells and their inflammatory niche from the colorectal precancerous adenoma stage to the cancerous stage: Mechanisms and clinical implications
Guanglin Cui, Ziqi Wang, Hanzhe Liu, Zhigang Pang
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piRNAs and PIWI proteins: From biogenesis to their role in cancer
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Gene Reports.2021; 22: 101013. CrossRef
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Identification of Genomic Alterations of Perineural Invasion in Patients with Stage II Colorectal Cancer

Hao Su, Chen Chang, Jiajie Hao, Xin Xu, Mandula Bao, Shou Luo, Chuanduo Zhao, Qian Liu, Xishan Wang, Zhixiang Zhou, Haitao Zhou
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Molecular and Functional Characterization of the Somatic PIWIL1/piRNA Pathway in Colorectal Cancer Cells
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Differential expression of PIWIL2 in papillary thyroid cancers
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High expression of PIWIL2 promotes tumor cell proliferation, migration and predicts a poor prognosis in glioma
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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.

Does the Colorectal Cancer Among Koreans Share the Same Pathological Features by Geographical Distribution: A Nationwide Survey of Surgically Resected 1,676 Cancers from 1,602 Patients.: Mee Soo Chang, Jin Hee Sohn, Dae Young Kang, Gyeong Hoon Kang, Myung Sook Kim, Woo Ho Kim, Jong Hee Nam, Woo Sung Moon, Sun Hoo Park, Cheol Jeun Park, Ro hyun Sung, Young Lyun Oh, Eun Sook Chang, Hee Kyung Chang, Mee Yon Cho, Kyung Ja Cho, Yong Il Kim; Korean J Pathol. 2001;35(1):14-19.

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Abstract PDF: BACKGROUND
This nationwide survey was undertaken to characterize the general pathological features of colorectal cancer in Korea, and especially to elucidate the geographical characteristics by means of their anatomical distribution.
METHODS
We analysed 1,676 colorectal cancers (from 1,602 patients) surgically resected in 1998 at 15 institutions from nine geographical sites in Korea.
RESULTS
The topographic incidence of colorectal cancer in seven out of the total nine geographical sites, was the highest in the rectum (32-54%); and those from Wonju and Cheongju were in the sigmoid colon (28% for both). The right colon cancer incidence was 42% in Wonju and 36% in Cheongju, while it was 17-22% in the other areas. The cecal cancer incidences in Wonju and in Taegu were 7% and 8%, respectively, but 0-4% in the other areas. As for histology, moderately differentiated adenocarcinoma was the most frequent (46-84%), except for in Wonju and Chonju, where the most predominant type was well differentiated (63% and 52%, respectively).
CONCLUSION
The incidence of right colon cancer was higher in Wonju and Cheongju, than in the other geographical sites. The cecal predilection was prominent in Taegu and Wonju. The Elucidation of geographical differences in degree of differentiation for tubular adenocarcinoma seems to require further cumulative study with strict guidelines.

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.

Assessment of Apoptosis by M30 Immunoreactivity and the Relationship with the MSI status and the Clinicopathological Characteristics of Colorectal Carcinomas.: Hyun Jeong Kang, Mee Young Sol, Do Youn Park, Soo Han Lee, Dong Hun Shin, Jee Yeon Kim, Kyung Un Choi, Hwal Woong Kim, Chang Hun Lee, Gi Young Huh; Korean J Pathol. 2006;40(5):319-325.

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Abstract PDF: BACKGROUND
The monoclonal antibody M30 recognizes a neoepitope of cytokeratin 18 that's produced during the process of apoptosis, and it is reactive in formalin-fixed, paraffin-embedded tissue. The detailed nature of apoptosis in colorectal cancer is unclear, especially in regard to the MSI status and the clinicopathologic factors. The purpose of this study was to elucidate the apoptosis assessed by M30 immunoreactivity in colorectal cancer and its relationship with the MSI status and the various clinicopathologic factors of colorectal cancers.
METHODS
101 colorectal cancers were classified according to levels of MSI as 12 MSI-H, 4 MSI-L and 85 MSS. Apoptosis was quantified by immunohistochemistry with using M30 CytoDEATH anti-body.
RESULTS
The apoptotic index assessed by M30 was significantly increased in the MSI-H and MSI-L colorectal cancer compared to that in the MSS colorectal cancer. Right sided colon cancer showed a significant higher apoptotic index than did the left sided colon cancer. There was also a tendency for decreased apoptosis in metastatic colorectal cancers (Duke's stage D). There was somewhat of an increase of apoptosis in colorectal cancers with mucinous carcinoma and medullary carcinoma, and also in the colorectal cancers with an increased TIL count, but this was not statistically significant.
CONCLUSION
M30 immunoreactivity is a valuable method to detect apoptosis in formalin-fixed, paraffin-embedded tissue and it might explain that MSI-H colorectal cancer shows better clinical behavior than MSS colorectal cancer in regard to the increased apoptosis.

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