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- Transglutaminase 2 Expression and Its Prognostic Significance in Clear Cell Renal Cell Carcinoma
- Min Jee Park, Hae Woon Baek, Ye-Young Rhee, Cheol Lee, Jeong Whan Park, Hwal Woong Kim, Kyung Chul Moon
- J Pathol Transl Med. 2015;49(1):37-43. Published online January 15, 2015
- DOI: https://doi.org/10.4132/jptm.2014.10.25
- 8,834 View
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- 15 Web of Science
- 17 Crossref
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Abstract
PDF - Background
A few recent studies have demonstrated a possible role of transglutaminase 2 (TG2) in tumorigenesis or progression of renal cell carcinoma (RCC). The aim of this study was to examine TG2 expression and its clinicopathologic significance in a large number of human clear cell RCCs (CCRCCs). Methods: We analyzed 638 CCRCC patients who underwent partial or radical nephrectomy between 1995 and 2005. The expression of TG2 was determined by immunohistochemistry and categorized into four groups, according to staining intensity: negative (0), mild (1+), moderate (2+), and strong (3+). Results: TG2 staining intensity was negative in 8.5% of CCRCC (n=54), 1+ in 32.6% (n=208), 2+ in 50.5% (n=322), and 3+ in 8.5% (n=54). Strong TG2 expression was correlated with high Fuhrman nuclear grade (p=.011), high T category (p=.049), metastasis (p=.043) and male sex (p<.001) but not with N category.The survival analysis showed a significant association between strong TG2 expression and worse overall and cancer-specific survival (p=.027 and p=.010, respectively). On multivariate analysis, strong TG2 expression was a marginally significant prognostic indicator for Fuhrman nuclear grade and TNM staging (p=.054). Conclusions: Our study is the first to demonstrate the clinicopathologic significance of TG2 expression in a large number of human CCRCC samples. Strong TG2 expression was associated with high nuclear grade and poor prognosis. -
Citations
Citations to this article as recorded by
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Ga-Ram Kim, Joon Hee Kang, Hyeon Joo Kim, Eunji Im, Jinsu Bae, Woo Sun Kwon, Sun Young Rha, Hyun Cheol Chung, Eun Yi Cho, Soo-Youl Kim, Yong-Chul Kim
Bioorganic Chemistry.2024; 143: 107061. CrossRef - Transglutaminase 2 is associated with adverse colorectal cancer survival and represents a therapeutic target
Patrizia Malkomes, Ilaria Lunger, Elsie Oppermann, Johannes Lorenz, Sara Fatima Faqar-Uz-Zaman, Jiaoyan Han, Sabrina Bothur, Paul Ziegler, Katrin Bankov, Peter Wild, Wolf Otto Bechstein, Michael A. Rieger
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Silvia Muccioli, Valentina Brillo, Tatiana Varanita, Federica Rossin, Elisabetta Zaltron, Angelo Velle, Giorgia Alessio, Beatrice Angi, Filippo Severin, Anna Tosi, Manuela D’Eletto, Luca Occhigrossi, Laura Falasca, Vanessa Checchetto, Roberto Ciaccio, Ame
Cell Death & Disease.2023;[Epub] CrossRef - The role of transglutaminase 2 in regulation of the balance between autophagy and apoptosis in tumor cells
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International Journal of Molecular Sciences.2022; 23(9): 4475. CrossRef - The Biological and Biomechanical Role of Transglutaminase-2 in the Tumour Microenvironment
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Cancers.2021; 13(11): 2788. CrossRef - A Precision Strategy to Cure Renal Cell Carcinoma by Targeting Transglutaminase 2
Soo-Youl Kim, Jeffrey W. Keillor
International Journal of Molecular Sciences.2020; 21(7): 2493. CrossRef - Evaluation of nuclear NF-κB, transglutaminase2, and ERCC1 as predictors of platinum resistance in testicular tumors
Alan A. Azambuja, Paula Engroff, Bruna T. Silva, Roberta C. S. Zorzetti, Fernanda B. Morrone
International braz j urol.2020; 46(3): 353. CrossRef - Transglutaminase 2-Mediated p53 Depletion Promotes Angiogenesis by Increasing HIF-1α-p300 Binding in Renal Cell Carcinoma
Seon-Hyeong Lee, Joon Hee Kang, Ji Sun Ha, Jae-Seon Lee, Su-Jin Oh, Hyun-Jung Choi, Jaewhan Song, Soo-Youl Kim
International Journal of Molecular Sciences.2020; 21(14): 5042. CrossRef - Role of Tissue Transglutaminase Catalytic and Guanosine Triphosphate-Binding Domains in Renal Cell Carcinoma Progression
Burge Ulukan, Ajna Bihorac, Tarik Sipahioglu, Robert Kiraly, Laszlo Fesus, Dilek Telci
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Molecular Carcinogenesis.2019; 58(6): 837. CrossRef - Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus
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Amino Acids.2018; 50(11): 1583. CrossRef - Renal Cell Carcinoma Is Abrogated by p53 Stabilization through Transglutaminase 2 Inhibition
Seon-Hyeong Lee, Won-Kyu Lee, Nayeon Kim, Joon Hee Kang, Kyung-Hee Kim, Seul-Gi Kim, Jae-Seon Lee, Soohyun Lee, Jongkook Lee, Jungnam Joo, Woo Sun Kwon, Sun Young Rha, Soo-Youl Kim
Cancers.2018; 10(11): 455. CrossRef - Tissue transglutaminase expression is necessary for adhesion, metastatic potential and cancer stemness of renal cell carcinoma
Yesim Bagatur, Ayca Zeynep Ilter Akulke, Ajna Bihorac, Merve Erdem, Dilek Telci
Cell Adhesion & Migration.2017; : 1. CrossRef - Characterization of clear cell renal cell carcinoma by gene expression profiling
Bryan J. Thibodeau, Matthew Fulton, Laura E. Fortier, Timothy J. Geddes, Barbara L. Pruetz, Samreen Ahmed, Amy Banes-Berceli, Ping L. Zhang, George D. Wilson, Jason Hafron
Urologic Oncology: Seminars and Original Investigations.2016; 34(4): 168.e1. CrossRef - Prognostic role of tissue transglutaminase 2 in colon carcinoma
María Jesús Fernández-Aceñero, Sofía Torres, Irene Garcia-Palmero, Cristina Díaz del Arco, J. Ignacio Casal
Virchows Archiv.2016; 469(6): 611. CrossRef
- Discovery of novel 1H-benzo[d]imidazole-4,7-dione based transglutaminase 2 inhibitors as p53 stabilizing anticancer agents in renal cell carcinoma
- The Effect of Dehydroepiandrosterone on Inhibition of Carcinogenesis and Induction of Apoptosis in Murine Hepatoma Model.
- Kye Yong Song, Eun Sup Park, Jee young Choi, Sang Chul Park
- Korean J Pathol. 1995;29(1):24-32.
- 1,442 View
- 12 Download
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Abstract
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- Tumor suppressive effect of dehydroepiandrosterone (DHEA) on the experimentally induced hepatocellular carcinoma was investigated, especially focusing on glutatione transferase and transglutaminase with aptosis in the carcinogenesis. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into AA group treated by the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-acetamidofluorene (AAF) and AD group treated with DHEA simultaneously with AAF and the AAD group treated by DHEA after treatment with AAF. Each group was divided by time sequence further into four subgroups, GI (8wk), G2 (16wk), G3 (28wk), and G4 (36wk). For neoplastic lesion, the immuno histochemical study with anti GSTP antibody was carried out, while the activity and expression of TGase was compared at the same time. The results were summarized as follows; GST-P positive foci detected in AD groups were significantly more suppressed by DHEA treatment than AA groups (P<0.05). AD groups. AD group showed higher activities of TGase than AA groups (P<0.05), which was confirmed by Western and Northern blot analysis. But the number of apoptotic bodies was not correlated with activity and expression of TGase in the nodule. These results suggest that the suppressive effect of DHEA on the murine hepatocellular carcinogenesis might be operating on the promotion process of carcinogenesis rather than regression process of transformed hyperplastic nodules.
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