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

Abstract 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 adjustin...

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Autores principales:	Hye Eun Park, Seung-Yeon Yoo, Nam-Yun Cho, Jeong Mo Bae, Sae-Won Han, Hye Seung Lee, Kyu Joo Park, Tae-You Kim, Gyeong Hoon Kang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/758520450d43498cae6072e4621baaf6
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spelling	oai:doaj.org-article:758520450d43498cae6072e4621baaf62021-12-02T18:30:57ZTumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX10.1038/s41598-021-94044-42045-2322https://doaj.org/article/758520450d43498cae6072e4621baaf62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94044-4https://doaj.org/toc/2045-2322Abstract 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.Hye Eun ParkSeung-Yeon YooNam-Yun ChoJeong Mo BaeSae-Won HanHye Seung LeeKyu Joo ParkTae-You KimGyeong Hoon KangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hye Eun Park Seung-Yeon Yoo Nam-Yun Cho Jeong Mo Bae Sae-Won Han Hye Seung Lee Kyu Joo Park Tae-You Kim Gyeong Hoon Kang Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX
description	Abstract 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.
format	article
author	Hye Eun Park Seung-Yeon Yoo Nam-Yun Cho Jeong Mo Bae Sae-Won Han Hye Seung Lee Kyu Joo Park Tae-You Kim Gyeong Hoon Kang
author_facet	Hye Eun Park Seung-Yeon Yoo Nam-Yun Cho Jeong Mo Bae Sae-Won Han Hye Seung Lee Kyu Joo Park Tae-You Kim Gyeong Hoon Kang
author_sort	Hye Eun Park
title	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_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_sort	tumor microenvironment-adjusted prognostic implications of the kras mutation subtype in patients with stage iii colorectal cancer treated with adjuvant folfox
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/758520450d43498cae6072e4621baaf6
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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

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