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Immune-related gene expression signatures in colorectal cancer
The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strateg...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157333/ https://www.ncbi.nlm.nih.gov/pubmed/34079596 http://dx.doi.org/10.3892/ol.2021.12804 |
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author | Sun, Zhenqing Xia, Wei Lyu, Yali Song, Yanan Wang, Min Zhang, Ruirui Sui, Guode Li, Zhenlu Song, Li Wu, Changliang Liew, Choong-Chin Yu, Lei Cheng, Guang Cheng, Changming |
author_facet | Sun, Zhenqing Xia, Wei Lyu, Yali Song, Yanan Wang, Min Zhang, Ruirui Sui, Guode Li, Zhenlu Song, Li Wu, Changliang Liew, Choong-Chin Yu, Lei Cheng, Guang Cheng, Changming |
author_sort | Sun, Zhenqing |
collection | PubMed |
description | The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (PPP3R1), amyloid β precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with ‘adaptive immune responses’, ‘innate immune responses’ and ‘cytokine signaling’. The survival analysis found that a high level of PPP3R1 expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between PPP3R1 expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy. |
format | Online Article Text |
id | pubmed-8157333 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-81573332021-06-01 Immune-related gene expression signatures in colorectal cancer Sun, Zhenqing Xia, Wei Lyu, Yali Song, Yanan Wang, Min Zhang, Ruirui Sui, Guode Li, Zhenlu Song, Li Wu, Changliang Liew, Choong-Chin Yu, Lei Cheng, Guang Cheng, Changming Oncol Lett Articles The immune system is crucial in regulating colorectal cancer (CRC) tumorigenesis. Identification of immune-related transcriptomic signatures derived from the peripheral blood of patients with CRC would provide insights into CRC pathogenesis, and suggest novel clues to potential immunotherapy strategies for the disease. The present study collected blood samples from 59 patients with CRC and 62 healthy control patients and performed whole blood gene expression profiling using microarray hybridization. Immune-related gene expression signatures for CRC were identified from immune gene datasets, and an algorithmic predictive model was constructed for distinguishing CRC from controls. Model performance was characterized using an area under the receiver operating characteristic curve (ROC AUC). Functional categories for CRC-specific gene expression signatures were determined using gene set enrichment analyses. A Kaplan-Meier plotter survival analysis was also performed for CRC-specific immune genes in order to characterize the association between gene expression and CRC prognosis. The present study identified five CRC-specific immune genes [protein phosphatase 3 regulatory subunit Bα (PPP3R1), amyloid β precursor protein, cathepsin H, proteasome activator subunit 4 and DEAD-Box Helicase 3 X-Linked]. A predictive model based on this five-gene panel showed good discriminatory power (independent test set sensitivity, 83.3%; specificity, 94.7%, accuracy, 89.2%; ROC AUC, 0.96). The candidate genes were involved in pathways associated with ‘adaptive immune responses’, ‘innate immune responses’ and ‘cytokine signaling’. The survival analysis found that a high level of PPP3R1 expression was associated with a poor CRC prognosis. The present study identified five CRC-specific immune genes that were potential diagnostic biomarkers for CRC. The biological function analysis indicated a close association between CRC pathogenesis and the immune system, and may reveal more information about the immunogenic and pathogenic mechanisms driving CRC in the future. Overall, the association between PPP3R1 expression and survival of patients with CRC revealed potential new targets for CRC immunotherapy. D.A. Spandidos 2021-07 2021-05-20 /pmc/articles/PMC8157333/ /pubmed/34079596 http://dx.doi.org/10.3892/ol.2021.12804 Text en Copyright: © Sun et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Sun, Zhenqing Xia, Wei Lyu, Yali Song, Yanan Wang, Min Zhang, Ruirui Sui, Guode Li, Zhenlu Song, Li Wu, Changliang Liew, Choong-Chin Yu, Lei Cheng, Guang Cheng, Changming Immune-related gene expression signatures in colorectal cancer |
title | Immune-related gene expression signatures in colorectal cancer |
title_full | Immune-related gene expression signatures in colorectal cancer |
title_fullStr | Immune-related gene expression signatures in colorectal cancer |
title_full_unstemmed | Immune-related gene expression signatures in colorectal cancer |
title_short | Immune-related gene expression signatures in colorectal cancer |
title_sort | immune-related gene expression signatures in colorectal cancer |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157333/ https://www.ncbi.nlm.nih.gov/pubmed/34079596 http://dx.doi.org/10.3892/ol.2021.12804 |
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