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Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX

Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the...

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Autores principales: Park, Hye Eun, Yoo, Seung-Yeon, Cho, Nam-Yun, Bae, Jeong Mo, Han, Sae-Won, Lee, Hye Seung, Park, Kyu Joo, Kim, Tae-You, Kang, Gyeong Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285533/
https://www.ncbi.nlm.nih.gov/pubmed/34272423
http://dx.doi.org/10.1038/s41598-021-94044-4
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author Park, Hye Eun
Yoo, Seung-Yeon
Cho, Nam-Yun
Bae, Jeong Mo
Han, Sae-Won
Lee, Hye Seung
Park, Kyu Joo
Kim, Tae-You
Kang, Gyeong Hoon
author_facet Park, Hye Eun
Yoo, Seung-Yeon
Cho, Nam-Yun
Bae, Jeong Mo
Han, Sae-Won
Lee, Hye Seung
Park, Kyu Joo
Kim, Tae-You
Kang, Gyeong Hoon
author_sort Park, Hye Eun
collection PubMed
description Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the tumor-infiltrating lymphocytes (TIL) and tumor-stromal percentage (TSP) statuses. In two independent cohorts, KRAS mutations were analyzed by Sanger sequencing and/or next-generation sequencing. TIL density and the TSP were quantified from whole-slide immunohistochemical images. KRAS-mutant CRCs were divided into three subgroups (G12D/V, other codon 12 mutations and codon 13 mutations) to examine their differential effect on TIL density, the TSP and recurrence-free survival (RFS). Among the KRAS mutations, only the G12D/V subgroups showed significantly less TIL infiltration than the wild-type CRCs. According to survival analysis, G12D/V mutations were associated with short RFS; codon 13 mutations showed discordant trends in the two cohorts, and other codon 12 mutations showed no significant association. Multivariate analysis further supported the prognostic value of G12D/V mutations. This result is not only consistent with a recent study suggesting the immunosuppressive effect of mutant KRAS but also provides insight into the type-specific prognostic effect of KRAS mutations.
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spelling pubmed-82855332021-07-21 Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX Park, Hye Eun Yoo, Seung-Yeon Cho, Nam-Yun Bae, Jeong Mo Han, Sae-Won Lee, Hye Seung Park, Kyu Joo Kim, Tae-You Kang, Gyeong Hoon Sci Rep Article Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the tumor-infiltrating lymphocytes (TIL) and tumor-stromal percentage (TSP) statuses. In two independent cohorts, KRAS mutations were analyzed by Sanger sequencing and/or next-generation sequencing. TIL density and the TSP were quantified from whole-slide immunohistochemical images. KRAS-mutant CRCs were divided into three subgroups (G12D/V, other codon 12 mutations and codon 13 mutations) to examine their differential effect on TIL density, the TSP and recurrence-free survival (RFS). Among the KRAS mutations, only the G12D/V subgroups showed significantly less TIL infiltration than the wild-type CRCs. According to survival analysis, G12D/V mutations were associated with short RFS; codon 13 mutations showed discordant trends in the two cohorts, and other codon 12 mutations showed no significant association. Multivariate analysis further supported the prognostic value of G12D/V mutations. This result is not only consistent with a recent study suggesting the immunosuppressive effect of mutant KRAS but also provides insight into the type-specific prognostic effect of KRAS mutations. Nature Publishing Group UK 2021-07-16 /pmc/articles/PMC8285533/ /pubmed/34272423 http://dx.doi.org/10.1038/s41598-021-94044-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Park, Hye Eun
Yoo, Seung-Yeon
Cho, Nam-Yun
Bae, Jeong Mo
Han, Sae-Won
Lee, Hye Seung
Park, Kyu Joo
Kim, Tae-You
Kang, Gyeong Hoon
Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
title Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
title_full Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
title_fullStr Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
title_full_unstemmed Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
title_short Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
title_sort tumor microenvironment-adjusted prognostic implications of the kras mutation subtype in patients with stage iii colorectal cancer treated with adjuvant folfox
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285533/
https://www.ncbi.nlm.nih.gov/pubmed/34272423
http://dx.doi.org/10.1038/s41598-021-94044-4
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