Circulating Tumor DNA Detection by Digital-Droplet PCR in Pancreatic Ductal Adenocarcinoma: A Systematic Review

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2021 Mar 6

PMID 33673558

Citations 28

Authors

Marisol Huerta

Susana Rosello

Luis Sabater

Ana Ferrer

Noelia Tarazona

Desamparados Roda

Valentina Gambardella

Clara Alfaro-Cervello

Marina Garces-Albir

Andres Cervantes

Maider Ibarrola-Villava

Affiliations

Soon will be listed here.

Abstract

Pancreatic cancer (PC) is one of the most devastating malignant tumors, being the seventh leading cause of cancer-related death worldwide. Researchers and clinicians are endeavoring to develop strategies for the early detection of the disease and the improvement of treatment results. Adequate biopsy is still challenging because of the pancreas's poor anatomic location. Recently, circulating tumor DNA (ctDNA) could be identified as a liquid biopsy tool with huge potential as a non-invasive biomarker in early diagnosis, prognosis and management of PC. ctDNA is released from apoptotic and necrotic cancer cells, as well as from living tumor cells and even circulating tumor cells, and it can reveal genetic and epigenetic alterations with tumor-specific and individual mutation and methylation profiles. However, ctDNA sensibility remains a limitation and the accuracy of ctDNA as a biomarker for PC is relatively low and cannot be currently used as a screening or diagnostic tool. Increasing evidence suggests that ctDNA is an interesting biomarker for predictive or prognosis studies, evaluating minimal residual disease, longitudinal follow-up and treatment management. Promising results have been published and therefore the objective of our review is to understand the current role and the future perspectives of ctDNA in PC.

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References

Lin M, Alnaggar M, Liang S, Chen J, Xu K, Dong S . Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer. Cell Physiol Biochem. 2018; 47(4):1556-1564. DOI: 10.1159/000490874. View

Cohen J, Javed A, Thoburn C, Wong F, Tie J, Gibbs P . Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers. Proc Natl Acad Sci U S A. 2017; 114(38):10202-10207. PMC: 5617273. DOI: 10.1073/pnas.1704961114. View

Hussung S, Follo M, Klar R, Michalczyk S, Fritsch K, Nollmann F . Development and Clinical Validation of Discriminatory Multitarget Digital Droplet PCR Assays for the Detection of Hot Spot KRAS and NRAS Mutations in Cell-Free DNA. J Mol Diagn. 2020; 22(7):943-956. DOI: 10.1016/j.jmoldx.2020.04.206. View

Guibert N, Pradines A, Farella M, Casanova A, Gouin S, Keller L . Monitoring KRAS mutations in circulating DNA and tumor cells using digital droplet PCR during treatment of KRAS-mutated lung adenocarcinoma. Lung Cancer. 2016; 100:1-4. DOI: 10.1016/j.lungcan.2016.07.021. View

Fernandez-Del Castillo C . A Changing Landscape in Pancreatic Cancer. Ann Surg. 2018; 268(1):9-10. DOI: 10.1097/SLA.0000000000002755. View

Sefrioui D, Blanchard F, Toure E, Basile P, Beaussire L, Dolfus C . Diagnostic value of CA19.9, circulating tumour DNA and circulating tumour cells in patients with solid pancreatic tumours. Br J Cancer. 2017; 117(7):1017-1025. PMC: 5625666. DOI: 10.1038/bjc.2017.250. View

Hadano N, Murakami Y, Uemura K, Hashimoto Y, Kondo N, Nakagawa N . Prognostic value of circulating tumour DNA in patients undergoing curative resection for pancreatic cancer. Br J Cancer. 2016; 115(1):59-65. PMC: 4931379. DOI: 10.1038/bjc.2016.175. View

Poruk K, Gay D, Brown K, Mulvihill J, Boucher K, Scaife C . The clinical utility of CA 19-9 in pancreatic adenocarcinoma: diagnostic and prognostic updates. Curr Mol Med. 2013; 13(3):340-51. PMC: 4419808. DOI: 10.2174/1566524011313030003. View

Shapiro B, Chakrabarty M, COHN E, Leon S . Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer. 1983; 51(11):2116-20. DOI: 10.1002/1097-0142(19830601)51:11<2116::aid-cncr2820511127>3.0.co;2-s. View

10.

Alcaide M, Cheung M, Bushell K, Arthur S, Wong H, Karasinska J . A Novel Multiplex Droplet Digital PCR Assay to Identify and Quantify KRAS Mutations in Clinical Specimens. J Mol Diagn. 2018; 21(2):214-227. DOI: 10.1016/j.jmoldx.2018.09.007. View

11.

Rice A, Del Rio Hernandez A . The Mutational Landscape of Pancreatic and Liver Cancers, as Represented by Circulating Tumor DNA. Front Oncol. 2019; 9:952. PMC: 6769086. DOI: 10.3389/fonc.2019.00952. View

12.

Tjensvoll K, Lapin M, Buhl T, Oltedal S, Steen-Ottosen Berry K, Gilje B . Clinical relevance of circulating KRAS mutated DNA in plasma from patients with advanced pancreatic cancer. Mol Oncol. 2016; 10(4):635-43. PMC: 5423145. DOI: 10.1016/j.molonc.2015.11.012. View

13.

Woo S, Kim M, Joo J, Yoon K, Park B, Park S . Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost-Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study. Cancer Res Treat. 2017; 49(4):1022-1032. PMC: 5654154. DOI: 10.4143/crt.2016.495. View

14.

Li M, Diehl F, Dressman D, Vogelstein B, Kinzler K . BEAMing up for detection and quantification of rare sequence variants. Nat Methods. 2006; 3(2):95-7. DOI: 10.1038/nmeth850. View

15.

Yamada T, Nakamori S, Ohzato H, Oshima S, Aoki T, Higaki N . Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res. 1998; 4(6):1527-32. View

16.

McDermott G, Do D, Litterst C, Maar D, Hindson C, Steenblock E . Multiplexed target detection using DNA-binding dye chemistry in droplet digital PCR. Anal Chem. 2013; 85(23):11619-27. DOI: 10.1021/ac403061n. View

17.

Guo S, Shi X, Shen J, Gao S, Wang H, Shen S . Preoperative detection of KRAS G12D mutation in ctDNA is a powerful predictor for early recurrence of resectable PDAC patients. Br J Cancer. 2020; 122(6):857-867. PMC: 7078253. DOI: 10.1038/s41416-019-0704-2. View

18.

Hong D, Fakih M, Strickler J, Desai J, Durm G, Shapiro G . KRAS Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020; 383(13):1207-1217. PMC: 7571518. DOI: 10.1056/NEJMoa1917239. View

19.

Cohen J, Li L, Wang Y, Thoburn C, Afsari B, Danilova L . Detection and localization of surgically resectable cancers with a multi-analyte blood test. Science. 2018; 359(6378):926-930. PMC: 6080308. DOI: 10.1126/science.aar3247. View

20.

Michaelidou K, Koutoulaki C, Mavridis K, Vorrias E, Papadaki M, Koutsopoulos A . Detection of G12/G13 Mutations in Cell Free-DNA by Droplet Digital PCR, Offers Prognostic Information for Patients with Advanced Non-Small Cell Lung Cancer. Cells. 2020; 9(11). PMC: 7699710. DOI: 10.3390/cells9112514. View