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Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer
Studies have demonstrated that non–MSI-H/pMMR colorectal cancer (CRC) has a worse prognosis and relapse rate than microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) CRC. Hence, searching for a novel tool to advance the prognostic management of non–MSI-H/pMMR CRC is vital. In th...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891566/ https://www.ncbi.nlm.nih.gov/pubmed/35252170 http://dx.doi.org/10.3389/fcell.2022.790214 |
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author | Liu, Zaoqu Xu, Hui Ge, Xiaoyong Weng, Siyuan Dang, Qin Han, Xinwei |
author_facet | Liu, Zaoqu Xu, Hui Ge, Xiaoyong Weng, Siyuan Dang, Qin Han, Xinwei |
author_sort | Liu, Zaoqu |
collection | PubMed |
description | Studies have demonstrated that non–MSI-H/pMMR colorectal cancer (CRC) has a worse prognosis and relapse rate than microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) CRC. Hence, searching for a novel tool to advance the prognostic management of non–MSI-H/pMMR CRC is vital. In this study, using three independent public cohorts and a clinical in-house cohort, we developed and validated a microsatellite stable–associated signature (MSSAS). The initial signature establishment was performed in GSE39582 (n = 454). This was followed by independent validation of this signature in The Cancer Genome Atlas–CRC (n = 312), GSE39084 (n = 54), and in-house cohort (n = 146). As a result, MSSAS was proven to be an independent risk factor for overall survival and relapse-free survival in non–MSI-H/pMMR CRC. Receiver operating characteristic analysis showed that MSSAS had a stable and accurate performance in all cohorts for 1, 3, and 5 years, respectively. Further analysis suggested that MSSAS performed better than age, gender, and the T, N, M, and AJCC stages, adjuvant chemotherapy, tumor mutation burden, neoantigen, and TP53, KRAS, BRAF, and PIK3CA mutations. The clinical validation was executed to further ensure the robustness and clinical feasibility of this signature. In conclusion, MSSAS might be a robust and promising biomarker for advancing clinical management of non–MSI-H/pMMR CRC. |
format | Online Article Text |
id | pubmed-8891566 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88915662022-03-04 Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer Liu, Zaoqu Xu, Hui Ge, Xiaoyong Weng, Siyuan Dang, Qin Han, Xinwei Front Cell Dev Biol Cell and Developmental Biology Studies have demonstrated that non–MSI-H/pMMR colorectal cancer (CRC) has a worse prognosis and relapse rate than microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) CRC. Hence, searching for a novel tool to advance the prognostic management of non–MSI-H/pMMR CRC is vital. In this study, using three independent public cohorts and a clinical in-house cohort, we developed and validated a microsatellite stable–associated signature (MSSAS). The initial signature establishment was performed in GSE39582 (n = 454). This was followed by independent validation of this signature in The Cancer Genome Atlas–CRC (n = 312), GSE39084 (n = 54), and in-house cohort (n = 146). As a result, MSSAS was proven to be an independent risk factor for overall survival and relapse-free survival in non–MSI-H/pMMR CRC. Receiver operating characteristic analysis showed that MSSAS had a stable and accurate performance in all cohorts for 1, 3, and 5 years, respectively. Further analysis suggested that MSSAS performed better than age, gender, and the T, N, M, and AJCC stages, adjuvant chemotherapy, tumor mutation burden, neoantigen, and TP53, KRAS, BRAF, and PIK3CA mutations. The clinical validation was executed to further ensure the robustness and clinical feasibility of this signature. In conclusion, MSSAS might be a robust and promising biomarker for advancing clinical management of non–MSI-H/pMMR CRC. Frontiers Media S.A. 2022-02-17 /pmc/articles/PMC8891566/ /pubmed/35252170 http://dx.doi.org/10.3389/fcell.2022.790214 Text en Copyright © 2022 Liu, Xu, Ge, Weng, Dang and Han. https://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 | Cell and Developmental Biology Liu, Zaoqu Xu, Hui Ge, Xiaoyong Weng, Siyuan Dang, Qin Han, Xinwei Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer |
title | Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer |
title_full | Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer |
title_fullStr | Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer |
title_full_unstemmed | Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer |
title_short | Gene Expression Profile Reveals a Prognostic Signature of Non–MSI-H/pMMR Colorectal Cancer |
title_sort | gene expression profile reveals a prognostic signature of non–msi-h/pmmr colorectal cancer |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891566/ https://www.ncbi.nlm.nih.gov/pubmed/35252170 http://dx.doi.org/10.3389/fcell.2022.790214 |
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