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Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer

The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated usin...

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Autores principales: Yang, Sheng, Liu, Tong, Cheng, Yanping, Bai, Yunfei, Liang, Geyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890448/
https://www.ncbi.nlm.nih.gov/pubmed/31605436
http://dx.doi.org/10.1111/cas.14216
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author Yang, Sheng
Liu, Tong
Cheng, Yanping
Bai, Yunfei
Liang, Geyu
author_facet Yang, Sheng
Liu, Tong
Cheng, Yanping
Bai, Yunfei
Liang, Geyu
author_sort Yang, Sheng
collection PubMed
description The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse‐free survival in training, validation, and entire cohorts (P < .05). In addition, PIS provided a higher net benefit than TNM stage. A composite nomogram was built based on PIS and patients' clinical information with well‐fitted calibration curves (c‐index = 0.84). We further used other cohorts from Gene Expression Omnibus databases and obtained similar results, confirming the reliability and validity of the DIS and PIS. In addition, the unsupervised clustering analysis using immune cell proportions revealed 6 immune subtypes, suggesting that the immune types defined as having relatively high levels of M0 or/and M1 macrophages were the high‐risk subtypes of relapse. In conclusion, this study comprehensively analyzed the tumor immune microenvironment and identified DIS and PIS for digestive system cancers.
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spelling pubmed-68904482019-12-12 Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer Yang, Sheng Liu, Tong Cheng, Yanping Bai, Yunfei Liang, Geyu Cancer Sci Original Articles The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse‐free survival in training, validation, and entire cohorts (P < .05). In addition, PIS provided a higher net benefit than TNM stage. A composite nomogram was built based on PIS and patients' clinical information with well‐fitted calibration curves (c‐index = 0.84). We further used other cohorts from Gene Expression Omnibus databases and obtained similar results, confirming the reliability and validity of the DIS and PIS. In addition, the unsupervised clustering analysis using immune cell proportions revealed 6 immune subtypes, suggesting that the immune types defined as having relatively high levels of M0 or/and M1 macrophages were the high‐risk subtypes of relapse. In conclusion, this study comprehensively analyzed the tumor immune microenvironment and identified DIS and PIS for digestive system cancers. John Wiley and Sons Inc. 2019-11-02 2019-12 /pmc/articles/PMC6890448/ /pubmed/31605436 http://dx.doi.org/10.1111/cas.14216 Text en © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Yang, Sheng
Liu, Tong
Cheng, Yanping
Bai, Yunfei
Liang, Geyu
Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
title Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
title_full Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
title_fullStr Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
title_full_unstemmed Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
title_short Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
title_sort immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890448/
https://www.ncbi.nlm.nih.gov/pubmed/31605436
http://dx.doi.org/10.1111/cas.14216
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