Diagnostic and Prognostic Value of Circulating Cell-Free DNA for Cholangiocarcinoma

被引：29

作者：

Wintachai, Preawwalee ^{[1
,2
]}

Lim, Jing Quan ^{[3
,4
]}

Techasen, Anchalee ^{[2
,5
]}

Lert-Itthiporn, Worachart ^{[6
]}

Kongpetch, Sarinya ^{[2
,7
]}

Loilome, Watcharin ^{[2
,6
]}

Chindaprasirt, Jarin ^{[2
,8
]}

Titapun, Attapol ^{[2
,9
]}

Namwat, Nisana ^{[2
,6
]}

Khuntikeo, Narong ^{[2
,9
]}

Jusakul, Apinya ^{[2
,5
]}

机构：

[1] Khon Kaen Univ, Grad Sch, Biomed Sci Program, Khon Kaen 40002, Thailand

[2] Khon Kaen Univ, Cholangiocarcinoma Res Inst, Khon Kaen 40002, Thailand

[3] Natl Canc Ctr, Div Med Oncol, Lymphoma Genom Translat Res Lab, Singapore 169857, Singapore

[4] Duke NUS Med Sch, Singapore 169857, Singapore

[5] Khon Kaen Univ, Fac Associated Med Sci, Ctr Res & Dev Med Diagnost Labs, Khon Kaen 40002, Thailand

[6] Khon Kaen Univ, Fac Med, Dept Biochem, Khon Kaen 40002, Thailand

[7] Khon Kaen Univ, Fac Med, Dept Pharmacol, Khon Kaen 40002, Thailand

[8] Khon Kaen Univ, Fac Med, Dept Internal Med, Khon Kaen 40002, Thailand

[9] Khon Kaen Univ, Fac Med, Dept Surg, Khon Kaen 40002, Thailand

来源：

DIAGNOSTICS | 2021年 / 11卷 / 06期

关键词：

bile duct cancer; cell-free DNA; circulating tumor DNA; prognosis; diagnosis; liquid biopsy; sequencing; TUMOR DNA; CANCER; MARKER; BLOOD; INFECTION; PATTERNS; MUTATION; CA19-9; GENOME; PBRM1;

D O I：

10.3390/diagnostics11060999

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The analysis of cfDNA has been applied as a liquid biopsy in several malignancies. However, its value in the diagnosis and prognosis of cholangiocarcinoma (CCA) have not been well defined. We aimed to investigate the diagnostic and prognostic values of cfDNA level and tumor-specific mutation in circulating DNA (ctDNA) in CCA. The plasma cfDNA levels from 62 CCA patients, 33 benign biliary disease (BBD) patients and 30 normal controls were quantified by fluorescent assay. Targeted probe-based sequencing of 60 genes was applied for mutation profiling in 10 ctDNA samples and their corresponding treatment-naive tissues. cfDNA levels in CCA were significantly higher than those in BBD and normal controls. We found that cfDNA levels at 0.2175 and 0.3388 ng/mu L significantly discriminated CCA from healthy controls and BBD with 88.7 and 82.3% sensitivity and 96.7 and 57.6% specificity, respectively. cfDNA levels showed superior diagnostic efficacy in detecting CCA compared to CEA and CA19-9. ARID1A (30%), PBRM1 (30%), MTOR (30%), and FGFR3 (30%) mutations were the most common. Using nine frequently mutated genes in the ctDNA samples, the diagnostic accuracy of cfDNA sequencing was 90.8%, with 96.7% average sensitivity and 72.4% specificity. This study supports the use of cfDNA as a diagnosis and prognostic biomarker for CCA.

引用

页数：19

共 62 条

[1] Cholangiocarcinoma 2020: the next horizon in mechanisms and management [J].

Banales, Jesus M. ;

Marin, Jose J. G. ;

Lamarca, Angela ;

Rodrigues, Pedro M. ;

Khan, Shahid A. ;

Roberts, Lewis R. ;

Cardinale, Vincenzo ;

Carpino, Guido ;

Andersen, Jesper B. ;

Braconi, Chiara ;

Calvisi, Diego F. ;

Perugorria, Maria J. ;

Fabris, Luca ;

Boulter, Luke ;

Macias, Rocio I. R. ;

Gaudio, Eugenio ;

Alvaro, Domenico ;

Gradilone, Sergio A. ;

Strazzabosco, Mario ;

Marzioni, Marco ;

Coulouarn, Cedric ;

Fouassier, Laura ;

Raggi, Chiara ;

Invernizzi, Pietro ;

Mertens, Joachim C. ;

Moncsek, Anja ;

Rizvi, Sumera ;

Heimbach, Julie ;

Koerkamp, Bas Groot ;

Bruix, Jordi ;

Forner, Alejandro ;

Bridgewater, John ;

Valle, Juan W. ;

Gores, Gregory J. .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2020, 17 (09) :557-588

[2] Detection of Circulating Tumor DNA in Early- and Late-Stage Human Malignancies [J].

Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

Fecher, Leslie A. ;

Gallia, Gary L. ;

Gibbs, Peter ;

Le, Dung ;

Giuntoli, Robert L. ;

Goggins, Michael ;

Hogarty, Michael D. ;

Holdhoff, Matthias ;

Hong, Seung-Mo ;

Jiao, Yuchen ;

Juhl, Hartmut H. ;

Kim, Jenny J. ;

Siravegna, Giulia ;

Laheru, Daniel A. ;

Lauricella, Calogero ;

Lim, Michael ;

Lipson, Evan J. ;

Marie, Suely Kazue Nagahashi ;

Netto, George J. ;

Oliner, Kelly S. ;

Olivi, Alessandro ;

Olsson, Louise ;

Riggins, Gregory J. ;

Sartore-Bianchi, Andrea ;

Schmidt, Kerstin ;

Shih, Ie-Ming ;

Oba-Shinjo, Sueli Mieko ;

Siena, Salvatore ;

Theodorescu, Dan ;

Tie, Jeanne ;

Harkins, Timothy T. ;

Veronese, Silvio ;

Wang, Tian-Li ;

Weingart, Jon D. .

SCIENCE TRANSLATIONAL MEDICINE, 2014, 6 (224)

[3] Cholangiocarcinoma: Current Knowledge and New Developments [J].

Blechacz, Boris .

GUT AND LIVER, 2017, 11 (01) :13-26

[4] Cholangiocarcinoma: Current opinion on clinical practice diagnostic and therapeutic algorithms A review of the literature and a long-standing experience of a referral center [J].

Brandi, Giovanni ;

Venturia, Michela ;

Pantaleo, Maria Abbondanza ;

Ercolani, Giorgio .

DIGESTIVE AND LIVER DISEASE, 2016, 48 (03) :231-241

[5] Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma [J].

Cambridge, William A. ;

Fairfield, Cameron ;

Powell, James J. ;

Harrison, Ewen M. ;

Soreide, Kjetil ;

Wigmore, Stephen J. ;

Guest, Rachel, V .

ANNALS OF SURGERY, 2021, 273 (02) :240-250

[6] Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers [J].

Chan-on, Waraporn ;

Nairismaegi, Maarja-Liisa ;

Ong, Choon Kiat ;

Lim, Weng Khong ;

Dima, Simona ;

Pairojkul, Chawalit ;

Lim, Kiat Hon ;

McPherson, John R. ;

Cutcutache, Ioana ;

Heng, Hong Lee ;

Ooi, London ;

Chung, Alexander ;

Chow, Pierce ;

Cheow, Peng Chung ;

Lee, Ser Yee ;

Choo, Su Pin ;

Tan, Iain Bee Huat ;

Duda, Dan ;

Nastase, Anca ;

Myint, Swe Swe ;

Wong, Bernice Huimin ;

Gan, Anna ;

Rajasegaran, Vikneswari ;

Ng, Cedric Chuan Young ;

Nagarajan, Sanjanaa ;

Jusakul, Apinya ;

Zhang, Shenli ;

Vohra, Priya ;

Yu, Willie ;

Huang, DaChuan ;

Sithithaworn, Paiboon ;

Yongvanit, Puangrat ;

Wongkham, Sopit ;

Khuntikeo, Narong ;

Bhudhisawasdi, Vajaraphongsa ;

Popescu, Irinel ;

Rozen, Steven G. ;

Tan, Patrick ;

Teh, Bin Tean .

NATURE GENETICS, 2013, 45 (12) :1474-U100

[7] wANNOVAR: annotating genetic variants for personal genomes via the web [J].

Chang, Xiao ;

Wang, Kai .

JOURNAL OF MEDICAL GENETICS, 2012, 49 (07) :433-436

[8] fastp: an ultra-fast all-in-one FASTQ preprocessor [J].

Chen, Shifu ;

Zhou, Yanqing ;

Chen, Yaru ;

Gu, Jia .

BIOINFORMATICS, 2018, 34 (17) :884-890

[9] Detection and localization of surgically resectable cancers with a multi-analyte blood test [J].

Cohen, Joshua D. ;

Li, Lu ;

Wang, Yuxuan ;

Thoburn, Christopher ;

Afsari, Bahman ;

Danilova, Ludmila ;

Douville, Christopher ;

Javed, Ammar A. ;

Wong, Fay ;

Mattox, Austin ;

Hruban, Ralph. H. ;

Wolfgang, Christopher L. ;

Goggins, Michael G. ;

Dal Molin, Marco ;

Wang, Tian-Li ;

Roden, Richard ;

Klein, Alison P. ;

Ptak, Janine ;

Dobbyn, Lisa ;

Schaefer, Joy ;

Silliman, Natalie ;

Popoli, Maria ;

Vogelstein, Joshua T. ;

Browne, James D. ;

Schoen, Robert E. ;

Brand, Randall E. ;

Tie, Jeanne ;

Gibbs, Peter ;

Wong, Hui-Li ;

Mansfield, Aaron S. ;

Jen, Jin ;

Hanash, Samir M. ;

Falconi, Massimo ;

Allen, Peter J. ;

Zhou, Shibin ;

Bettegowda, Chetan ;

Diaz, Luis A., Jr. ;

Tomasetti, Cristian ;

Kinzler, Kenneth W. ;

Vogelstein, Bert ;

Lennon, Anne Marie ;

Papadopoulos, Nickolas .

SCIENCE, 2018, 359 (6378) :926-+

[10] Activation of mammalian target of rapamycin complex 1 (mTORC1) and Raf/Pyk2 by growth factor-mediated Eph receptor 2 (EphA2) is required for cholangiocarcinoma growth and metastasis [J].

Cui, Xiang-Dan ;

Lee, Mi-Jin ;

Kim, Jong-Hyun ;

Hao, Pei-Pei ;

Liu, Lan ;

Yu, Goung-Ran ;

Kim, Dae-Ghon .

HEPATOLOGY, 2013, 57 (06) :2248-2260

← 1 2 3 4 5 6 7 →