ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer

Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well ev...

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Main Authors: In Hye Song, Young-Ae Kim, Sun-Hee Heo, In Ah Park, Miseon Lee, Won Seon Bang, Hye Seon Park, Gyungyub Gong, Hee Jin Lee
Format: Article
Language:English
Published: SAGE Publishing 2017-10-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317734816
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author In Hye Song
Young-Ae Kim
Sun-Hee Heo
In Ah Park
Miseon Lee
Won Seon Bang
Hye Seon Park
Gyungyub Gong
Hee Jin Lee
author_facet In Hye Song
Young-Ae Kim
Sun-Hee Heo
In Ah Park
Miseon Lee
Won Seon Bang
Hye Seon Park
Gyungyub Gong
Hee Jin Lee
author_sort In Hye Song
collection DOAJ
description Tumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data. Among the 681 triple-negative breast cancer patients, 45.8% demonstrated high ADAR1 expression. Tumours with high ADAR1 expression exhibited high tumour-infiltrating lymphocyte levels, considerable CD8 + T lymphocyte infiltration, high histological grade and high expression of interferon-related proteins, including HLA-ABC, MxA and PKR. Among patients with lymph node metastasis, those with high tumour-infiltrating lymphocyte levels and low ADAR1 expression demonstrated the best disease-free survival. The Cancer Genome Atlas data analysis of basal-like tumours revealed significant positive correlation between ADAR1 and CD8B expression and positive association of high ADAR1 expression with immune responses and apoptosis pathways. We detected high ADAR1 expression in half of the triple-negative breast cancer patients. In addition to DNA mutations, RNA editing can be related to neoantigens; hence, we need to explore non-synonymous mutations exclusively found using RNA sequencing data to identify clinically relevant neoantigens.
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spelling doaj-art-32126db0fdd144bb88ed88dd3fae18842025-08-20T03:33:01ZengSAGE PublishingTumor Biology1423-03802017-10-013910.1177/1010428317734816ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancerIn Hye Song0Young-Ae Kim1Sun-Hee Heo2In Ah Park3Miseon Lee4Won Seon Bang5Hye Seon Park6Gyungyub Gong7Hee Jin Lee8Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaDepartment of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaDepartment of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaAsan Center for Cancer Genome Discovery, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaDepartment of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaDepartment of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, KoreaTumours with a high mutation burden exhibit considerable neoantigens and tumour-infiltrating lymphocytes. RNA editing by ADAR1 is a source of changes in epitope. However, ADAR1 expression in cancer cells and tumour-infiltrating lymphocyte levels in triple-negative breast cancer have not been well evaluated. We immunohistochemically examined ADAR1 expression in 681 triple-negative breast cancer patients and analysed their clinicopathological characteristics. We also analysed basal-like tumours using The Cancer Genome Atlas data. Among the 681 triple-negative breast cancer patients, 45.8% demonstrated high ADAR1 expression. Tumours with high ADAR1 expression exhibited high tumour-infiltrating lymphocyte levels, considerable CD8 + T lymphocyte infiltration, high histological grade and high expression of interferon-related proteins, including HLA-ABC, MxA and PKR. Among patients with lymph node metastasis, those with high tumour-infiltrating lymphocyte levels and low ADAR1 expression demonstrated the best disease-free survival. The Cancer Genome Atlas data analysis of basal-like tumours revealed significant positive correlation between ADAR1 and CD8B expression and positive association of high ADAR1 expression with immune responses and apoptosis pathways. We detected high ADAR1 expression in half of the triple-negative breast cancer patients. In addition to DNA mutations, RNA editing can be related to neoantigens; hence, we need to explore non-synonymous mutations exclusively found using RNA sequencing data to identify clinically relevant neoantigens.https://doi.org/10.1177/1010428317734816
spellingShingle In Hye Song
Young-Ae Kim
Sun-Hee Heo
In Ah Park
Miseon Lee
Won Seon Bang
Hye Seon Park
Gyungyub Gong
Hee Jin Lee
ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer
Tumor Biology
title ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer
title_full ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer
title_fullStr ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer
title_full_unstemmed ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer
title_short ADAR1 expression is associated with tumour-infiltrating lymphocytes in triple-negative breast cancer
title_sort adar1 expression is associated with tumour infiltrating lymphocytes in triple negative breast cancer
url https://doi.org/10.1177/1010428317734816
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