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Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer

BACKGROUND: Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5‐methylcytosine (m(5)C) is an important posttranscriptional widespread modification involved in many biological processes. However, the association between genetic variations of m(5)C...

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Autores principales: Chen, Silu, Cao, Xiangming, Ben, Shuai, Zhu, Lingjun, Gu, Dongying, Wu, Yuan, Li, Shuwei, Yu, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883553/
https://www.ncbi.nlm.nih.gov/pubmed/35861369
http://dx.doi.org/10.1002/cam4.5018
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author Chen, Silu
Cao, Xiangming
Ben, Shuai
Zhu, Lingjun
Gu, Dongying
Wu, Yuan
Li, Shuwei
Yu, Qiang
author_facet Chen, Silu
Cao, Xiangming
Ben, Shuai
Zhu, Lingjun
Gu, Dongying
Wu, Yuan
Li, Shuwei
Yu, Qiang
author_sort Chen, Silu
collection PubMed
description BACKGROUND: Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5‐methylcytosine (m(5)C) is an important posttranscriptional widespread modification involved in many biological processes. However, the association between genetic variations of m(5)C modification genes and the prognostic value of colorectal cancer remains unclear. METHODS: We investigated the association between candidate single nucleotide polymorphisms (SNPs) in 13 m(5)C modification genes and colorectal cancer overall survival (OS) after chemotherapy by the Cox regression model. The combined effect of selected SNPs on OS, progression‐free survival (PFS), and disease control rate (DCR) was assessed by the number of risk alleles (NRA). The GTEx and TCGA database were used to perform expression qualitative trait locus (eQTL) analysis. RESULTS: We identified that two SNPs in YBX1 were associated with OS after chemotherapy (HR = 1.43, p = 0.001 for rs10890208; HR = 1.36, p = 0.025 for rs3862218). A striking dose–response effect between NRA and OS after chemotherapy was found (p (trend) = 0.002). The DCR of patients receiving oxaliplatin chemotherapy in the 3–4 NRA group was markedly reduced in comparison to that in the 0–2 NRA group (OR = 1.49, p = 0.036). Moreover, YBX1 mRNA expression was significantly overexpressed in tumor tissues (p < 0.05) in the TCGA database, and eQTL analysis demonstrated that the two SNPs were associated with YBX1 (p = 0.003 for rs10890208 and p = 0.024 for rs3862218). CONCLUSION: Our study indicates that genetic variants in m(5)C modification genes may mediate changes in YBX1 mRNA levels and affect the chemotherapeutic efficacy of colorectal cancer patients.
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spelling pubmed-98835532023-01-31 Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer Chen, Silu Cao, Xiangming Ben, Shuai Zhu, Lingjun Gu, Dongying Wu, Yuan Li, Shuwei Yu, Qiang Cancer Med RESEARCH ARTICLES BACKGROUND: Colorectal cancer is one of the most common malignant digestive tract tumors with a poor prognosis. RNA 5‐methylcytosine (m(5)C) is an important posttranscriptional widespread modification involved in many biological processes. However, the association between genetic variations of m(5)C modification genes and the prognostic value of colorectal cancer remains unclear. METHODS: We investigated the association between candidate single nucleotide polymorphisms (SNPs) in 13 m(5)C modification genes and colorectal cancer overall survival (OS) after chemotherapy by the Cox regression model. The combined effect of selected SNPs on OS, progression‐free survival (PFS), and disease control rate (DCR) was assessed by the number of risk alleles (NRA). The GTEx and TCGA database were used to perform expression qualitative trait locus (eQTL) analysis. RESULTS: We identified that two SNPs in YBX1 were associated with OS after chemotherapy (HR = 1.43, p = 0.001 for rs10890208; HR = 1.36, p = 0.025 for rs3862218). A striking dose–response effect between NRA and OS after chemotherapy was found (p (trend) = 0.002). The DCR of patients receiving oxaliplatin chemotherapy in the 3–4 NRA group was markedly reduced in comparison to that in the 0–2 NRA group (OR = 1.49, p = 0.036). Moreover, YBX1 mRNA expression was significantly overexpressed in tumor tissues (p < 0.05) in the TCGA database, and eQTL analysis demonstrated that the two SNPs were associated with YBX1 (p = 0.003 for rs10890208 and p = 0.024 for rs3862218). CONCLUSION: Our study indicates that genetic variants in m(5)C modification genes may mediate changes in YBX1 mRNA levels and affect the chemotherapeutic efficacy of colorectal cancer patients. John Wiley and Sons Inc. 2022-07-21 /pmc/articles/PMC9883553/ /pubmed/35861369 http://dx.doi.org/10.1002/cam4.5018 Text en © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle RESEARCH ARTICLES
Chen, Silu
Cao, Xiangming
Ben, Shuai
Zhu, Lingjun
Gu, Dongying
Wu, Yuan
Li, Shuwei
Yu, Qiang
Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer
title Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer
title_full Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer
title_fullStr Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer
title_full_unstemmed Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer
title_short Genetic variants in RNA m(5)C modification genes associated with survival and chemotherapy efficacy of colorectal cancer
title_sort genetic variants in rna m(5)c modification genes associated with survival and chemotherapy efficacy of colorectal cancer
topic RESEARCH ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883553/
https://www.ncbi.nlm.nih.gov/pubmed/35861369
http://dx.doi.org/10.1002/cam4.5018
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