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High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection
BACKGROUND: Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA) has a high immune response with chronic inflammation and oxidative stress. CD44 and Nestin, two cancer stem cell (CSC) markers, play major roles in cancer cell survival. Effects of immune response and expression CSC markers...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179826/ https://www.ncbi.nlm.nih.gov/pubmed/34103974 http://dx.doi.org/10.2147/IJGM.S306339 |
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author | Titapun, Attapol Luvira, Vor Srisuk, Tharatip Jareanrat, Apiwat Thanasukarn, Vasin Thanee, Malinee Sa-Ngiamwibool, Prakasit Padthaisong, Sureerat Duangkumpha, Kassaporn Suksawat, Manida Loilome, Watcharin Sithithaworn, Paiboon Techasen, Anchalee Thinkhamrop, Bandit Dzienny, Alexa Caglayan, Ayse Park, David Mahmud, Simran Khuntikeo, Narong |
author_facet | Titapun, Attapol Luvira, Vor Srisuk, Tharatip Jareanrat, Apiwat Thanasukarn, Vasin Thanee, Malinee Sa-Ngiamwibool, Prakasit Padthaisong, Sureerat Duangkumpha, Kassaporn Suksawat, Manida Loilome, Watcharin Sithithaworn, Paiboon Techasen, Anchalee Thinkhamrop, Bandit Dzienny, Alexa Caglayan, Ayse Park, David Mahmud, Simran Khuntikeo, Narong |
author_sort | Titapun, Attapol |
collection | PubMed |
description | BACKGROUND: Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA) has a high immune response with chronic inflammation and oxidative stress. CD44 and Nestin, two cancer stem cell (CSC) markers, play major roles in cancer cell survival. Effects of immune response and expression CSC markers on survival of patients with CCA remain unclear. OBJECTIVE: To investigate the effects of level of OV IgG together with CSC marker expression and also the combination of these markers on survival of CCA patients after curative resection. METHODS: All serum specimens from CCA patients who underwent curative surgery from 2005 to 2015 were examined for IgG for OV antigen by ELISA. Tissue specimens were studied for CD44 and Nestin expression. Survival analysis by Cox proportional hazard model was used for estimating hazard ratio (HR) with a 95% confidence interval (CI). RESULTS: In this study, 122 (69.3%) of 176 were positive for OV IgG, and 35 (19.9%) were considered to have high-positive OV IgG. CD44s positive expression was found in 54 (40%), CD44v6 high expression in 96 (69.6%), CD44v8-10 high expression in 87 (63.5%) and Nestin high expression in 21 (16.1%). Multivariate survival analysis found that high-positive OV IgG and late stage tumor were independent prognostic factors with the adjusted HR of 2.24 (95% CI 1.27–3.93) and 2.78 (95% CI 1.46–5.29), respectively. Subgroup analysis in early and late stage CCA showed that a combined positive OV IgG and CD44s expression with the high expression of CD44v8-10 had the significantly poorest prognosis with HR of 3.75 (95% CI 1.61–8.72) and HR of 1.76 (95% CI 1.02–3.03), respectively. CONCLUSION: A high level of OV IgG as well as a high level of CSC markers resulted in an aggressive CCA. OV IgG level together with CSC markers can be used as the prognostic markers for CCA patients’ survival. The study of the CD44 pathway is promising for adjuvant treatment. |
format | Online Article Text |
id | pubmed-8179826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-81798262021-06-07 High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection Titapun, Attapol Luvira, Vor Srisuk, Tharatip Jareanrat, Apiwat Thanasukarn, Vasin Thanee, Malinee Sa-Ngiamwibool, Prakasit Padthaisong, Sureerat Duangkumpha, Kassaporn Suksawat, Manida Loilome, Watcharin Sithithaworn, Paiboon Techasen, Anchalee Thinkhamrop, Bandit Dzienny, Alexa Caglayan, Ayse Park, David Mahmud, Simran Khuntikeo, Narong Int J Gen Med Original Research BACKGROUND: Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA) has a high immune response with chronic inflammation and oxidative stress. CD44 and Nestin, two cancer stem cell (CSC) markers, play major roles in cancer cell survival. Effects of immune response and expression CSC markers on survival of patients with CCA remain unclear. OBJECTIVE: To investigate the effects of level of OV IgG together with CSC marker expression and also the combination of these markers on survival of CCA patients after curative resection. METHODS: All serum specimens from CCA patients who underwent curative surgery from 2005 to 2015 were examined for IgG for OV antigen by ELISA. Tissue specimens were studied for CD44 and Nestin expression. Survival analysis by Cox proportional hazard model was used for estimating hazard ratio (HR) with a 95% confidence interval (CI). RESULTS: In this study, 122 (69.3%) of 176 were positive for OV IgG, and 35 (19.9%) were considered to have high-positive OV IgG. CD44s positive expression was found in 54 (40%), CD44v6 high expression in 96 (69.6%), CD44v8-10 high expression in 87 (63.5%) and Nestin high expression in 21 (16.1%). Multivariate survival analysis found that high-positive OV IgG and late stage tumor were independent prognostic factors with the adjusted HR of 2.24 (95% CI 1.27–3.93) and 2.78 (95% CI 1.46–5.29), respectively. Subgroup analysis in early and late stage CCA showed that a combined positive OV IgG and CD44s expression with the high expression of CD44v8-10 had the significantly poorest prognosis with HR of 3.75 (95% CI 1.61–8.72) and HR of 1.76 (95% CI 1.02–3.03), respectively. CONCLUSION: A high level of OV IgG as well as a high level of CSC markers resulted in an aggressive CCA. OV IgG level together with CSC markers can be used as the prognostic markers for CCA patients’ survival. The study of the CD44 pathway is promising for adjuvant treatment. Dove 2021-06-01 /pmc/articles/PMC8179826/ /pubmed/34103974 http://dx.doi.org/10.2147/IJGM.S306339 Text en © 2021 Titapun et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Titapun, Attapol Luvira, Vor Srisuk, Tharatip Jareanrat, Apiwat Thanasukarn, Vasin Thanee, Malinee Sa-Ngiamwibool, Prakasit Padthaisong, Sureerat Duangkumpha, Kassaporn Suksawat, Manida Loilome, Watcharin Sithithaworn, Paiboon Techasen, Anchalee Thinkhamrop, Bandit Dzienny, Alexa Caglayan, Ayse Park, David Mahmud, Simran Khuntikeo, Narong High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection |
title | High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection |
title_full | High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection |
title_fullStr | High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection |
title_full_unstemmed | High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection |
title_short | High Levels of Serum IgG for Opisthorchis viverrini and CD44 Expression Predict Worse Prognosis for Cholangiocarcinoma Patients after Curative Resection |
title_sort | high levels of serum igg for opisthorchis viverrini and cd44 expression predict worse prognosis for cholangiocarcinoma patients after curative resection |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179826/ https://www.ncbi.nlm.nih.gov/pubmed/34103974 http://dx.doi.org/10.2147/IJGM.S306339 |
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