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Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals

Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different...

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Autores principales: Fan, Chuan-Wen, Kopsida, Maria, Liu, You-Bin, Zhang, Hong, Gao, Jing-Fang, Arbman, Gunnar, Cao, Si-Yu-Wei, Li, Yuan, Zhou, Zong-Guang, Sun, Xiao-Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979908/
https://www.ncbi.nlm.nih.gov/pubmed/32010608
http://dx.doi.org/10.3389/fonc.2019.01465
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author Fan, Chuan-Wen
Kopsida, Maria
Liu, You-Bin
Zhang, Hong
Gao, Jing-Fang
Arbman, Gunnar
Cao, Si-Yu-Wei
Li, Yuan
Zhou, Zong-Guang
Sun, Xiao-Feng
author_facet Fan, Chuan-Wen
Kopsida, Maria
Liu, You-Bin
Zhang, Hong
Gao, Jing-Fang
Arbman, Gunnar
Cao, Si-Yu-Wei
Li, Yuan
Zhou, Zong-Guang
Sun, Xiao-Feng
author_sort Fan, Chuan-Wen
collection PubMed
description Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC. Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively.
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spelling pubmed-69799082020-02-01 Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals Fan, Chuan-Wen Kopsida, Maria Liu, You-Bin Zhang, Hong Gao, Jing-Fang Arbman, Gunnar Cao, Si-Yu-Wei Li, Yuan Zhou, Zong-Guang Sun, Xiao-Feng Front Oncol Oncology Background: MRE11 plays an important role in DNA damage response for the maintenance of genome stability, and is becoming a prognostic marker for cancers, including colorectal cancer (CRC). However, the correlations of MRE11 to prognosis and tumor-infiltrating inflammatory cells (TIICs) in different locations of CRC remains unclear. Methods: Among Swedish and TCGA-COREAD patients, we investigated the association of MRE11 expression, tumor-infiltrating inflammatory cells (TIICs) and microsatellite status with survival in right-sided colon cancer (RSCC) and left-sided colon and rectal cancer (LSCRC). The signaling of MRE11-related was further analyzed using weighted gene co-expression network analysis and ClueGO. Results: High MRE11 expression alone or combination of high MRE11 expression with high TIICs was related to favorable prognosis in LSCRC. Moreover, high MRE11 expression was associated with favorable prognosis in LSCRC with microsatellite stability. The relationships above were adjusted for tumor stage, differentiation, and/or TIICs. However, no such evidence was observed in RSCC. Several signaling pathways involving MRE11 were found to be associated with cell cycle and DNA repair in RSCC and LSCRC, whereas, the activation of the immune response and necrotic cell death were specifically correlated with LSCRC. Conclusions: High MRE11 expression is an independent prognostic marker in LSCRC and enhanced prognostic potency of combining high MRE11 with high TIICs in LSCRC, mainly due to differential immune signaling activated by MRE11 in RSCC and LSCRC, respectively. Frontiers Media S.A. 2020-01-17 /pmc/articles/PMC6979908/ /pubmed/32010608 http://dx.doi.org/10.3389/fonc.2019.01465 Text en Copyright © 2020 Fan, Kopsida, Liu, Zhang, Gao, Arbman, Cao, Li, Zhou and Sun. 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
Fan, Chuan-Wen
Kopsida, Maria
Liu, You-Bin
Zhang, Hong
Gao, Jing-Fang
Arbman, Gunnar
Cao, Si-Yu-Wei
Li, Yuan
Zhou, Zong-Guang
Sun, Xiao-Feng
Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
title Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
title_full Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
title_fullStr Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
title_full_unstemmed Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
title_short Prognostic Heterogeneity of MRE11 Based on the Location of Primary Colorectal Cancer Is Caused by Activation of Different Immune Signals
title_sort prognostic heterogeneity of mre11 based on the location of primary colorectal cancer is caused by activation of different immune signals
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6979908/
https://www.ncbi.nlm.nih.gov/pubmed/32010608
http://dx.doi.org/10.3389/fonc.2019.01465
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