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

Cancers

Boram Park¹  Sun-Young Kong²  Wonyoung Choi²  Yun-Hee Kim²  Sung-Sik Han³  Woo Jin Lee³  Sang-Jae Park³  Sang Myung Woo³  Kyong-Ah Yoon⁴  Jae Hee Cho⁵  Jin-Hyeok Hwang⁶  Min Kyeong Kim⁷  Tae-Rim Lee⁸  Chang-Seok Ki⁸  Eun-Hae Cho⁸  Do Yei Kim⁸ 

[1] Biostatistics Collaboration Team, Research Core Center, Research Institute, National Cancer Center, Goyang 10408, Korea;Cancer Biomedical Science, National Cancer Center Graduate School of Cancer Science and Policy, Goyang 10408, Korea;Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang 10408, Korea;College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea;Department of Internal Medicine, Gachon University Gil Medical Center, Incheon 21556, Korea;Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea;Division of Translational Science, National Cancer Center, Goyang 10408, Korea;Genome Research Center, GC Genome, Yongin 16924, Korea;

关键词: pancreatic ductal adenocarcinoma;    genomic instability;    prognostic biomarker;    outcome prediction;    instability score;    circulating tumor DNA;   

DOI  :  10.3390/cancers13215466

来源: DOAJ

【 摘 要 】

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 (n = 110), locally advanced (n = 78), and metastatic (n = 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 (r² = 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.

【 授权许可】

Unknown