Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study

Genomic instability of circulating tumor DNA (ctDNA) as a prognostic biomarker has not been evaluated in pancreatic cancer. We investigated the role of the genomic instability index of ctDNA in pancreatic ductal adenocarcinoma (PDAC). We prospectively enrolled 315 patients newly diagnosed with resec...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sang Myung Woo, Min Kyeong Kim, Boram Park, Eun-Hae Cho, Tae-Rim Lee, Chang-Seok Ki, Kyong-Ah Yoon, Yun-Hee Kim, Wonyoung Choi, Do Yei Kim, Jin-Hyeok Hwang, Jae Hee Cho, Sung-Sik Han, Woo Jin Lee, Sang-Jae Park, Sun-Young Kong
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	pancreatic ductal adenocarcinoma genomic instability prognostic biomarker outcome prediction instability score circulating tumor DNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bf9fbe86bba14691a2b17839372df15f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:bf9fbe86bba14691a2b17839372df15f
record_format	dspace
spelling	oai:doaj.org-article:bf9fbe86bba14691a2b17839372df15f2021-11-11T15:33:34ZGenomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study10.3390/cancers132154662072-6694https://doaj.org/article/bf9fbe86bba14691a2b17839372df15f2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5466https://doaj.org/toc/2072-6694Genomic instability of circulating tumor DNA (ctDNA) as a prognostic biomarker has not been evaluated in pancreatic cancer. We investigated the role of the genomic instability index of ctDNA in pancreatic ductal adenocarcinoma (PDAC). We prospectively enrolled 315 patients newly diagnosed with resectable (<i>n</i> = 110), locally advanced (<i>n</i> = 78), and metastatic (<i>n</i> = 127) PDAC from March 2015 through January 2020. Low-depth whole-genome cell-free DNA sequencing identified genome-wide copy number alterations using instability score (I-score) to reflect genome-wide instability. Plasma cell-free and matched tumor tissue DNA from 15 patients with resectable pancreatic cancer was sequenced to assess the concordance of chromosomal copy number alteration profiles. Associations of I-score with clinical factors or survival were assessed. Seventy-six patients had high genomic instability with I-score > 7.3 in pre-treatment ctDNA; proportions of high I-score were 5.5%, 5.1%, and 52% in resectable, locally advanced, and metastatic stages, respectively. Correlation coefficients between Z-scores of plasma and tissue DNA at segment resolution were high (r<sup>2</sup> = 0.82). Univariable analysis showed the association of I-score with progression-free survival in each stage. Multivariable analyses demonstrated that clinical stage-adjusted I-scores were significant factors for progression-free and overall survival. In these patients, ctDNA genomic I-scores provided prognostic information relevant to progression-free survival in each clinical stage.Sang Myung WooMin Kyeong KimBoram ParkEun-Hae ChoTae-Rim LeeChang-Seok KiKyong-Ah YoonYun-Hee KimWonyoung ChoiDo Yei KimJin-Hyeok HwangJae Hee ChoSung-Sik HanWoo Jin LeeSang-Jae ParkSun-Young KongMDPI AGarticlepancreatic ductal adenocarcinomagenomic instabilityprognostic biomarkeroutcome predictioninstability scorecirculating tumor DNANeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5466, p 5466 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	pancreatic ductal adenocarcinoma genomic instability prognostic biomarker outcome prediction instability score circulating tumor DNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	pancreatic ductal adenocarcinoma genomic instability prognostic biomarker outcome prediction instability score circulating tumor DNA Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Sang Myung Woo Min Kyeong Kim Boram Park Eun-Hae Cho Tae-Rim Lee Chang-Seok Ki Kyong-Ah Yoon Yun-Hee Kim Wonyoung Choi Do Yei Kim Jin-Hyeok Hwang Jae Hee Cho Sung-Sik Han Woo Jin Lee Sang-Jae Park Sun-Young Kong Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study
description	Genomic instability of circulating tumor DNA (ctDNA) as a prognostic biomarker has not been evaluated in pancreatic cancer. We investigated the role of the genomic instability index of ctDNA in pancreatic ductal adenocarcinoma (PDAC). We prospectively enrolled 315 patients newly diagnosed with resectable (<i>n</i> = 110), locally advanced (<i>n</i> = 78), and metastatic (<i>n</i> = 127) PDAC from March 2015 through January 2020. Low-depth whole-genome cell-free DNA sequencing identified genome-wide copy number alterations using instability score (I-score) to reflect genome-wide instability. Plasma cell-free and matched tumor tissue DNA from 15 patients with resectable pancreatic cancer was sequenced to assess the concordance of chromosomal copy number alteration profiles. Associations of I-score with clinical factors or survival were assessed. Seventy-six patients had high genomic instability with I-score > 7.3 in pre-treatment ctDNA; proportions of high I-score were 5.5%, 5.1%, and 52% in resectable, locally advanced, and metastatic stages, respectively. Correlation coefficients between Z-scores of plasma and tissue DNA at segment resolution were high (r<sup>2</sup> = 0.82). Univariable analysis showed the association of I-score with progression-free survival in each stage. Multivariable analyses demonstrated that clinical stage-adjusted I-scores were significant factors for progression-free and overall survival. In these patients, ctDNA genomic I-scores provided prognostic information relevant to progression-free survival in each clinical stage.
format	article
author	Sang Myung Woo Min Kyeong Kim Boram Park Eun-Hae Cho Tae-Rim Lee Chang-Seok Ki Kyong-Ah Yoon Yun-Hee Kim Wonyoung Choi Do Yei Kim Jin-Hyeok Hwang Jae Hee Cho Sung-Sik Han Woo Jin Lee Sang-Jae Park Sun-Young Kong
author_facet	Sang Myung Woo Min Kyeong Kim Boram Park Eun-Hae Cho Tae-Rim Lee Chang-Seok Ki Kyong-Ah Yoon Yun-Hee Kim Wonyoung Choi Do Yei Kim Jin-Hyeok Hwang Jae Hee Cho Sung-Sik Han Woo Jin Lee Sang-Jae Park Sun-Young Kong
author_sort	Sang Myung Woo
title	Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study
title_short	Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study
title_full	Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study
title_fullStr	Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study
title_full_unstemmed	Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study
title_sort	genomic instability of circulating tumor dna as a prognostic marker for pancreatic cancer survival: a prospective cohort study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/bf9fbe86bba14691a2b17839372df15f
work_keys_str_mv	AT sangmyungwoo genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT minkyeongkim genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT borampark genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT eunhaecho genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT taerimlee genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT changseokki genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT kyongahyoon genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT yunheekim genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT wonyoungchoi genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT doyeikim genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT jinhyeokhwang genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT jaeheecho genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT sungsikhan genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT woojinlee genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT sangjaepark genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy AT sunyoungkong genomicinstabilityofcirculatingtumordnaasaprognosticmarkerforpancreaticcancersurvivalaprospectivecohortstudy
_version_	1718435208603107328

Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study

Ejemplares similares