A novel immune prognostic index for stratification of high-risk patients with early breast cancer

Abstract The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures ha...

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Main Authors: Hannah Lee, Mi Jeong Kwon, Beom-Mo Koo, Hee Geon Park, Jinil Han, Young Kee Shin
Format: Article
Language:English
Published: Nature Publishing Group 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-80274-5
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spelling doaj-54cdd1dd68c047778589e9532296be572021-01-10T12:47:50ZengNature Publishing GroupScientific Reports2045-23222021-01-0111111310.1038/s41598-020-80274-5A novel immune prognostic index for stratification of high-risk patients with early breast cancerHannah Lee0Mi Jeong Kwon1Beom-Mo Koo2Hee Geon Park3Jinil Han4Young Kee Shin5Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National UniversityCollege of Pharmacy, Kyungpook National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National UniversityDepartment of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National UniversityGencurix, Inc.Interdisciplinary Program in Bioinformatics, College of Natural Sciences, Seoul National UniversityAbstract The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.https://doi.org/10.1038/s41598-020-80274-5
collection DOAJ
language English
format Article
sources DOAJ
author Hannah Lee
Mi Jeong Kwon
Beom-Mo Koo
Hee Geon Park
Jinil Han
Young Kee Shin
spellingShingle Hannah Lee
Mi Jeong Kwon
Beom-Mo Koo
Hee Geon Park
Jinil Han
Young Kee Shin
A novel immune prognostic index for stratification of high-risk patients with early breast cancer
Scientific Reports
author_facet Hannah Lee
Mi Jeong Kwon
Beom-Mo Koo
Hee Geon Park
Jinil Han
Young Kee Shin
author_sort Hannah Lee
title A novel immune prognostic index for stratification of high-risk patients with early breast cancer
title_short A novel immune prognostic index for stratification of high-risk patients with early breast cancer
title_full A novel immune prognostic index for stratification of high-risk patients with early breast cancer
title_fullStr A novel immune prognostic index for stratification of high-risk patients with early breast cancer
title_full_unstemmed A novel immune prognostic index for stratification of high-risk patients with early breast cancer
title_sort novel immune prognostic index for stratification of high-risk patients with early breast cancer
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-01-01
description Abstract The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.
url https://doi.org/10.1038/s41598-020-80274-5
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