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Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma

OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA...

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Autores principales: Lee, Yong Hoon, Do, Sook Kyung, Lee, Shin Yup, Kang, Hyo-Gyoung, Choi, Jin Eun, Hong, Mi Jeong, Lee, Jang Hyuck, Lee, Sunwoong, Lee, Won Kee, Jeong, Ji Yun, Shin, Kyung Min, Park, Ji Eun, Choi, Sun Ha, Seo, Hyewon, Yoo, Seung Soo, Lee, Jaehee, Cha, Seung Ick, Kim, Chang Ho, Park, Jae Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: S. Karger AG 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932833/
https://www.ncbi.nlm.nih.gov/pubmed/36257285
http://dx.doi.org/10.1159/000527492
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author Lee, Yong Hoon
Do, Sook Kyung
Lee, Shin Yup
Kang, Hyo-Gyoung
Choi, Jin Eun
Hong, Mi Jeong
Lee, Jang Hyuck
Lee, Sunwoong
Lee, Won Kee
Jeong, Ji Yun
Shin, Kyung Min
Park, Ji Eun
Choi, Sun Ha
Seo, Hyewon
Yoo, Seung Soo
Lee, Jaehee
Cha, Seung Ick
Kim, Chang Ho
Park, Jae Yong
author_facet Lee, Yong Hoon
Do, Sook Kyung
Lee, Shin Yup
Kang, Hyo-Gyoung
Choi, Jin Eun
Hong, Mi Jeong
Lee, Jang Hyuck
Lee, Sunwoong
Lee, Won Kee
Jeong, Ji Yun
Shin, Kyung Min
Park, Ji Eun
Choi, Sun Ha
Seo, Hyewon
Yoo, Seung Soo
Lee, Jaehee
Cha, Seung Ick
Kim, Chang Ho
Park, Jae Yong
author_sort Lee, Yong Hoon
collection PubMed
description OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. RESULTS: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. CONCLUSION: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma.
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spelling pubmed-99328332023-02-17 Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma Lee, Yong Hoon Do, Sook Kyung Lee, Shin Yup Kang, Hyo-Gyoung Choi, Jin Eun Hong, Mi Jeong Lee, Jang Hyuck Lee, Sunwoong Lee, Won Kee Jeong, Ji Yun Shin, Kyung Min Park, Ji Eun Choi, Sun Ha Seo, Hyewon Yoo, Seung Soo Lee, Jaehee Cha, Seung Ick Kim, Chang Ho Park, Jae Yong Oncology Clinical Translational Research OBJECTIVE: This study was conducted to investigate the association between genetic variants in histone modification regions and clinical outcomes of PEM chemotherapy in patients with lung adenocarcinoma. METHODS: Potentially functional SNPs were selected using integrated analysis of ChIP-seq and RNA-seq. The associations of 279 SNPs with chemotherapy response and overall survival (OS) were analyzed in 314 lung adenocarcinoma patients who underwent PEM chemotherapy. RESULTS: Among the SNPs investigated, 18 were significantly associated with response to chemotherapy, while 28 with OS. Of these SNPs, rs549794A>G in an enhancer which is expected to regulate the expression of ribosomal protein S3 (RPS3) gene was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio = 0.59, 95% CI = 0.36–0.97, p = 0.04; adjusted hazard ratio = 1.44, 95% CI = 1.09–1.91, p = 0.01, respectively). Previous studies suggested that RPS3, a multi-functional protein with various extraribosomal activities, may play a role in chemotherapy resistance. Therefore, it is postulated that rs549794-induced change in the expression level of RPS3 may affect the response to PEM chemotherapy and consequently the survival outcomes in lung adenocarcinoma patients. CONCLUSION: This study suggests that genetic variants in the histone modification regions may be useful for the prediction of clinical outcomes of PEM chemotherapy in advanced lung adenocarcinoma. S. Karger AG 2023-02 2022-10-18 /pmc/articles/PMC9932833/ /pubmed/36257285 http://dx.doi.org/10.1159/000527492 Text en Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel https://creativecommons.org/licenses/by-nc/4.0/This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission.
spellingShingle Clinical Translational Research
Lee, Yong Hoon
Do, Sook Kyung
Lee, Shin Yup
Kang, Hyo-Gyoung
Choi, Jin Eun
Hong, Mi Jeong
Lee, Jang Hyuck
Lee, Sunwoong
Lee, Won Kee
Jeong, Ji Yun
Shin, Kyung Min
Park, Ji Eun
Choi, Sun Ha
Seo, Hyewon
Yoo, Seung Soo
Lee, Jaehee
Cha, Seung Ick
Kim, Chang Ho
Park, Jae Yong
Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
title Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
title_full Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
title_fullStr Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
title_full_unstemmed Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
title_short Genetic Variants in Histone Modification Regions Predict Clinical Outcomes of Pemetrexed Chemotherapy in Lung Adenocarcinoma
title_sort genetic variants in histone modification regions predict clinical outcomes of pemetrexed chemotherapy in lung adenocarcinoma
topic Clinical Translational Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9932833/
https://www.ncbi.nlm.nih.gov/pubmed/36257285
http://dx.doi.org/10.1159/000527492
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