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Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers
PURPOSE: The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs). MATERIALS AND METHODS: We measured the copy number of FGFR1 by droplet digital...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Korean Cancer Association
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962468/ https://www.ncbi.nlm.nih.gov/pubmed/31096734 http://dx.doi.org/10.4143/crt.2019.062 |
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author | Bae, Jeong Mo Wen, Xianyu Kim, Tae-Shin Kwak, Yoonjin Cho, Nam-Yun Lee, Hye Seung Kang, Gyeong Hoon |
author_facet | Bae, Jeong Mo Wen, Xianyu Kim, Tae-Shin Kwak, Yoonjin Cho, Nam-Yun Lee, Hye Seung Kang, Gyeong Hoon |
author_sort | Bae, Jeong Mo |
collection | PubMed |
description | PURPOSE: The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs). MATERIALS AND METHODS: We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs). RESULTS: CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification. CONCLUSION: FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs. |
format | Online Article Text |
id | pubmed-6962468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Korean Cancer Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-69624682020-01-22 Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers Bae, Jeong Mo Wen, Xianyu Kim, Tae-Shin Kwak, Yoonjin Cho, Nam-Yun Lee, Hye Seung Kang, Gyeong Hoon Cancer Res Treat Original Article PURPOSE: The purpose of this study was to reveal the clinicopathological characteristics and prognostic implications associated with fibroblast growth factor receptor 1 (FGFR1) amplification in colorectal cancers (CRCs). MATERIALS AND METHODS: We measured the copy number of FGFR1 by droplet digital polymerase chain reaction (ddPCR), and analyzed the FGFR1 expression by immunohistochemistry, in 764 surgically resected CRCs (SNUH2007 dataset, 384 CRCs; SNUH Folfox dataset, 380 CRCs). RESULTS: CRCs with ≥ 3.3 copies of the FGFR1 gene were classified as FGFR1 amplified. FGFR1 amplification was found in 10 of the 384 CRCs (2.6%) in the SNUH2007 dataset, and in 28 of the 380 CRCs (7.4%) in the SNUH Folfox dataset. In the SNUH2007 dataset, there was no association between the FGFR1 copy number status and sex, gross appearance, stage, or differentiation. High FGFR1 expression was associated with female sex and KRAS mutation. At the molecular level, FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, in both SNUH2007 and SNUH Folfox datasets. Survival analysis revealed that FGFR1 amplification was associated with significantly worse clinical outcome compared with no FGFR1 amplification, in both SNUH2007 and SNUH Folfox datasets. Within the SNUH2007 dataset, CRC patients with high FGFR1 expression had an inferior progression-free survival compared with those with low FGFR1 expression. The FGFR inhibitor, PD173074, repressed the proliferation of a CRC cell line overexpressing FGFR1, but not of cells with FGFR1 amplification. CONCLUSION: FGFR1 amplification measured by ddPCR can be a prognostic indicator of poor clinical outcome in patients with CRCs. Korean Cancer Association 2020-01 2019-05-08 /pmc/articles/PMC6962468/ /pubmed/31096734 http://dx.doi.org/10.4143/crt.2019.062 Text en Copyright © 2020 by the Korean Cancer Association This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Bae, Jeong Mo Wen, Xianyu Kim, Tae-Shin Kwak, Yoonjin Cho, Nam-Yun Lee, Hye Seung Kang, Gyeong Hoon Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers |
title | Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers |
title_full | Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers |
title_fullStr | Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers |
title_full_unstemmed | Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers |
title_short | Fibroblast Growth Factor Receptor 1 (FGFR1) Amplification Detected by Droplet Digital Polymerase Chain Reaction (ddPCR) Is a Prognostic Factor in Colorectal Cancers |
title_sort | fibroblast growth factor receptor 1 (fgfr1) amplification detected by droplet digital polymerase chain reaction (ddpcr) is a prognostic factor in colorectal cancers |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6962468/ https://www.ncbi.nlm.nih.gov/pubmed/31096734 http://dx.doi.org/10.4143/crt.2019.062 |
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