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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...

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Autores principales: Liu, Zaoqu, Xu, Hui, Ge, Xiaoyong, Weng, Siyuan, Dang, Qin, Han, Xinwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
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.
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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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