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Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma
Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. T...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883407/ https://www.ncbi.nlm.nih.gov/pubmed/31824841 http://dx.doi.org/10.3389/fonc.2019.01239 |
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author | Mehra, Siddharth Panwar, Rajesh Thakur, Bhaskar Yadav, Rajni Kumar, Manish Singh, Ratnakar Dash, Nihar Ranjan Sahni, Peush Chauhan, Shyam S. |
author_facet | Mehra, Siddharth Panwar, Rajesh Thakur, Bhaskar Yadav, Rajni Kumar, Manish Singh, Ratnakar Dash, Nihar Ranjan Sahni, Peush Chauhan, Shyam S. |
author_sort | Mehra, Siddharth |
collection | PubMed |
description | Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC. Methods: Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients (n = 43) and control subjects (n = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis. Results: The expression and activity of both CTSL and CTSB were significantly increased (p < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC (p < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC (p < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively. Conclusion: This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma. |
format | Online Article Text |
id | pubmed-6883407 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68834072019-12-10 Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma Mehra, Siddharth Panwar, Rajesh Thakur, Bhaskar Yadav, Rajni Kumar, Manish Singh, Ratnakar Dash, Nihar Ranjan Sahni, Peush Chauhan, Shyam S. Front Oncol Oncology Background: Gallbladder carcinoma (GBC) exhibits poor prognosis due to its detection at an advanced stage. Upregulation of lysosomal cysteine proteases cathepsin L (CTSL) and cathepsin B (CTSB) has been implicated in several tumorigenic processes. However, no such information in GBC was available. Therefore, the present study was planned to investigate the expression and clinical significance of these cathepsins in GBC. Methods: Activities of CTSL and CTSB were assayed in the gallbladder (GB) tissues obtained from GBC patients (n = 43) and control subjects (n = 69). Protein and mRNA levels were quantified using immunohistochemistry and real-time PCR (qPCR), respectively. Finally, serum levels of CTSL and CTSB were estimated by ELISA. Receiver operating characteristic (ROC) curve analysis was used for the assessment of sensitivity, specificity, and diagnostic accuracy of these cysteine cathepsins in GBC. The association of combined CTSL and CTSB activity with overall survival was assessed using Kaplan Meier survival analysis. Results: The expression and activity of both CTSL and CTSB were significantly increased (p < 0.050) in tumors of GBC patients as compared to controls. Enzymatic activity of CTSL+B and CTSB exhibited a strong positive association with tumor stage and lymph node involvement in GBC (p < 0.050). Interestingly, the elevated activity of combined CTSL+B was also associated with increased mortality in these patients. Furthermore, significantly enhanced levels of serum CTSL and CTSB were also observed in GBC (p < 0.050) as compared to controls. ROC analysis revealed high diagnostic significance of serum CTSB and CTSL for distinguishing GBC patients from controls with an area under the curve (AUC) of 82 and 77%, respectively. Conclusion: This study, for the first time, demonstrates the clinical significance of CTSL and CTSB overexpression in GBC. Our findings may help improve the clinical management of this carcinoma. Frontiers Media S.A. 2019-11-22 /pmc/articles/PMC6883407/ /pubmed/31824841 http://dx.doi.org/10.3389/fonc.2019.01239 Text en Copyright © 2019 Mehra, Panwar, Thakur, Yadav, Kumar, Singh, Dash, Sahni and Chauhan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Mehra, Siddharth Panwar, Rajesh Thakur, Bhaskar Yadav, Rajni Kumar, Manish Singh, Ratnakar Dash, Nihar Ranjan Sahni, Peush Chauhan, Shyam S. Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma |
title | Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma |
title_full | Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma |
title_fullStr | Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma |
title_full_unstemmed | Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma |
title_short | Expression and Clinical Implications of Cysteine Cathepsins in Gallbladder Carcinoma |
title_sort | expression and clinical implications of cysteine cathepsins in gallbladder carcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883407/ https://www.ncbi.nlm.nih.gov/pubmed/31824841 http://dx.doi.org/10.3389/fonc.2019.01239 |
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