scholarly journals Liquid Biopsy as a Prognostic and Theranostic Tool for the Management of Pancreatic Ductal Adenocarcinoma

2022 ◽  
Vol 8 ◽  
Author(s):  
Daniel C. Osei-Bordom ◽  
Gagandeep Sachdeva ◽  
Niki Christou

Pancreatic ductal adenocarcinomas (PDAC) represent one of the deadliest cancers worldwide. Survival is still low due to diagnosis at an advanced stage and resistance to treatment. Herein, we review the main types of liquid biopsy able to help in both prognosis and adaptation of treatments.

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1656 ◽  
Author(s):  
Etienne Buscail ◽  
Catherine Alix-Panabières ◽  
Pascaline Quincy ◽  
Thomas Cauvin ◽  
Alexandre Chauvet ◽  
...  

Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.


2021 ◽  
Vol Volume 14 ◽  
pp. 2163-2175
Author(s):  
Huilin Shao ◽  
Yue Zhang ◽  
Jie Yan ◽  
Xinchao Ban ◽  
Xiaojie Fan ◽  
...  

2020 ◽  
Vol 158 (6) ◽  
pp. S-857
Author(s):  
SOUVIK GHATAK ◽  
Satoshi Nishiwada ◽  
Eunsung Jun ◽  
Fuminori Sonohara ◽  
Yasuhiro Kodera ◽  
...  

2019 ◽  
Vol 156 (6) ◽  
pp. S-326-S-327
Author(s):  
Hiroyuki Terasawa ◽  
Hideaki Kinugasa ◽  
Kazuhiro Nouso ◽  
Soichiro Ako ◽  
Mami Hirai ◽  
...  

2019 ◽  
Vol 20 (10) ◽  
pp. 1348-1353 ◽  
Author(s):  
Hiroyuki Terasawa ◽  
Hideaki Kinugasa ◽  
Soichiro Ako ◽  
Mami Hirai ◽  
Hiroshi Matsushita ◽  
...  

2021 ◽  
Vol 160 (6) ◽  
pp. S-46
Author(s):  
Satoshi Nishiwada ◽  
Ya Cui ◽  
Masayuki Sho ◽  
Eunsung Jun ◽  
Takahiro Akahori ◽  
...  

2021 ◽  
Vol 22 (12) ◽  
pp. 6501
Author(s):  
Violeta Morcuende-Ventura ◽  
Sonia Hermoso-Durán ◽  
Natalia Abian-Franco ◽  
Roberto Pazo-Cid ◽  
Jorge L. Ojeda ◽  
...  

(1) Background: Biophysical techniques applied to serum samples characterization could promote the development of new diagnostic tools. Fluorescence spectroscopy has been previously applied to biological samples from cancer patients and differences from healthy individuals were observed. Dendronized hyperbranched polymers (DHP) based on bis(hydroxymethyl)propionic acid (bis-MPA) were developed in our group and their potential biomedical applications explored. (2) Methods: A total of 94 serum samples from diagnosed cancer patients and healthy individuals were studied (20 pancreatic ductal adenocarcinoma, 25 blood donor, 24 ovarian cancer, and 25 benign ovarian cyst samples). (3) Results: Fluorescence spectra of serum samples (fluorescence liquid biopsy, FLB) in the presence and the absence of DHP-bMPA were recorded and two parameters from the signal curves obtained. A secondary parameter, the fluorescence spectrum score (FSscore), was calculated, and the diagnostic model assessed. For pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer, the classification performance was improved when including DHP-bMPA, achieving high values of statistical sensitivity and specificity (over 85% for both pathologies). (4) Conclusions: We have applied FLB as a quick, simple, and minimally invasive promising technique in cancer diagnosis. The classification performance of the diagnostic method was further improved by using DHP-bMPA, which interacted differentially with serum samples from healthy and diseased subjects. These preliminary results set the basis for a larger study and move FLB closer to its clinical application, providing useful information for the oncologist during patient diagnosis.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Norihiko Sasaki ◽  
Kenichi Hirabayashi ◽  
Masaki Michishita ◽  
Kimimasa Takahashi ◽  
Fumio Hasegawa ◽  
...  

AbstractGangliosides, a group of glycosphingolipids, are known to be cell surface markers and functional factors in several cancers. However, the association between gangliosides and pancreatic ductal adenocarcinoma (PDAC) has not been well elucidated. In this study, we examined the expression and roles of ganglioside GM2 in PDAC. GM2+ cells showed a higher growth rate than GM2− cells in the adherent condition. When GM2– and GM2+ cells were cultured three-dimensionally, almost all cells in the spheres expressed GM2, including cancer stem cell (CSC)-like cells. A glycolipid synthesis inhibitor reduced GM2 expression and TGF-β1 signaling in these CSC-like cells, presumably by inhibiting the interaction between GM2 and TGFβ RII and suppressing invasion. Furthermore, suppression of GM2 expression by MAPK inhibition also reduced TGF-β1 signaling and suppressed invasion. GM2+ cells formed larger subcutaneous tumors at a high incidence in nude mice than did GM2– cells. In PDAC cases, GM2 expression was significantly associated with younger age, larger tumor size, advanced stage and higher histological grade. These findings suggest that GM2 could be used as a novel diagnostic and therapeutic target for PDAC.


Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 197 ◽  
Author(s):  
Moritz Reese ◽  
Isabelle Flammang ◽  
Zixuan Yang ◽  
Sameer A. Dhayat

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor entity, characterized by rapid disease progression, early metastatic dissemination, and late diagnosis at advanced tumor stages. Recently, we explored the clinical impact of several microRNAs (miR) associated with proliferation, epithelial-to-mesenchymal transition (EMT), and chemoresistance in tissue and blood serum specimens of PDAC patients. Here, we evaluated the potential of these miRs as diagnostic and prognostic biomarkers in PDAC in serum exosomes and their respective EpCAM-positive (epithelial cell adhesion molecule) subset. Expression analysis by RT-qRT-PCR (real-time quantitative reverse transcription polymerase chain reaction) revealed an overexpression of miR-200b and miR-200c in serum exosomes of PDAC patients as compared to healthy controls (p < 0.001; p = 0.024) and patients with chronic pancreatitis (p = 0.005; p = 0.19). Receiver operating characteristic (ROC) curve analysis showed that a biomarker panel consisting of miR-200b and miR-200c from total and EpCAM-positive serum exosomes enhanced the diagnostic accuracy of carbohydrate antigen 19-9 (CA.19-9) to 97% (p < 0.0001). Univariate survival analysis revealed a correlation between shorter overall survival (OS) and high expression of miR-200c in total serum exosomes (p = 0.038) and miR-200b in EpCAM-positive serum exosomes (p = 0.032), whereas EpCAM exosomal miR-200b was also indicative of shorter OS in the subgroup of patients treated with curative intent (p = 0.013). Multivariate survival analysis showed that miR-200b derived from EpCAM-positive serum exosomes might serve as an independent prognostic factor in PDAC (p = 0.044). Our findings indicate a potential role of exosomal miR-200 as diagnostic and prognostic liquid biopsy marker in PDAC and call for validation in a larger, multicenter setting.


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