scholarly journals Tumor-Specific miRNA Signatures in Combination with CA19−9 for Liquid Biopsy-Based Detection of PDAC

2021 ◽  
Vol 22 (24) ◽  
pp. 13621
Author(s):  
Min Woo Kim ◽  
Hani Koh ◽  
Jee Ye Kim ◽  
Suji Lee ◽  
Hyojung Lee ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is considered one of the most aggressive malignancies and has high mortality and poor survival rates. Therefore, there is an urgent need to discover non-invasive biomarkers for early detection before PDAC reaches the incurable stage. We hypothesized that liquid biopsy of PDAC-derived extracellular vesicles (PDEs) containing abundant microRNAs (miRNAs) could be used for early diagnosis of PDAC because they can be selectively enriched and because they are biologically stable. We isolated PDEs by immunocapture using magnetic beads, and we identified 13 miRNA candidates in 20 pancreatic cancer patients and 20 normal controls. We found that expression of five miRNAs, including miR−10b, miR−16, miR−155, miR−429, and miR−1290, was markedly higher in PDEs. Furthermore, the miRNA signatures along with serum carbohydrate antigen 19−9 (CA19−9) were optimized by logistic regression, and the miRNA signature and CA19−9 combination markers (CMs) were effective at differentiating PDAC patients from normal controls. As a result, the CMs represented a high sensitivity (AUC, 0.964; sensitivity, 100%; specificity, 80%) and a high specificity (AUC, 0.962; sensitivity, 85.71%; specificity, 100%). These findings suggest that five miRNAs expressed in PDEs and CA19−9 are valuable biomarkers for screening and diagnosis of pancreatic cancer by liquid biopsy.

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1986
Author(s):  
Victoria Heredia-Soto ◽  
Nuria Rodríguez-Salas ◽  
Jaime Feliu

Pancreatic ductal adenocarcinoma (PDAC) exhibits the poorest prognosis of all solid tumors, with a 5-year survival of less than 10%. To improve the prognosis, it is necessary to advance in the development of tools that help us in the early diagnosis, treatment selection, disease monitoring, evaluation of the response and prognosis. Liquid biopsy (LB), in its different modalities, represents a particularly interesting tool for these purposes, since it is a minimally invasive and risk-free procedure that can detect both the presence of genetic material from the tumor and circulating tumor cells (CTCs) in the blood and therefore distantly reflect the global status of the disease. In this work we review the current status of the main LB modalities (ctDNA, exosomes, CTCs and cfRNAs) for detecting and monitoring PDAC.


2017 ◽  
Vol 49 (4) ◽  
pp. 481-486 ◽  
Author(s):  
Pedro L. S. Usón Junior ◽  
Donato Callegaro-Filho ◽  
Diogo D. G. Bugano ◽  
Fernando Moura ◽  
Fernando C. Maluf

2016 ◽  
Vol 31 (2) ◽  
pp. 506-512 ◽  
Author(s):  
Kwang Hyun Chung ◽  
Ji Kon Ryu ◽  
Ban Seok Lee ◽  
Dong Kee Jang ◽  
Sang Hyub Lee ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 389
Author(s):  
Marwa Elsayed ◽  
Maen Abdelrahim

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in the US, and it is expected to be the second leading cause of cancer deaths by 2030. The lack of effective early screening tests and alarming symptoms with early undetectable micro-metastasis at the time of presentation play a vital role in the high death rate from pancreatic cancer. In addition to this, the low mutation burden in pancreatic cancer, low immunological profile, dense tumorigenesis stroma, and decreased tumor sensitivity to cytotoxic drugs contribute to the low survival rates in PDAC patients. Despite breakthroughs in chemotherapeutic and immunotherapeutic drugs, pancreatic cancer remains one of the solid tumors that exhibit meager curative rates. Therefore, researchers must dedicate more effort to understanding the pathology and immunological behavior of PDAC, in addition to properly utilizing more advanced screening modalities and new therapeutic agents. In our review, we focus mainly on the latest updates from clinical guidelines and novel therapies that have been recently investigated or are under investigation for PDAC. We used PubMed as a search tool for finding original research articles addressing the latest developments in diagnosing and treating PDAC. Additionally, we also used the clinical trials published on clinicaltrialsgov as sources for our data.


Cancers ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 6 ◽  
Author(s):  
Neus Martinez-Bosch ◽  
Judith Vinaixa ◽  
Pilar Navarro

Pancreatic ductal adenocarcinoma (PDA), the most frequent type of pancreatic cancer, remains one of the most challenging problems for the biomedical and clinical fields, with abysmal survival rates and poor therapy efficiency. Desmoplasia, which is abundant in PDA, can be blamed for much of the mechanisms behind poor drug performance, as it is the main source of the cytokines and chemokines that orchestrate rapid and silent tumor progression to allow tumor cells to be isolated into an extensive fibrotic reaction, which results in inefficient drug delivery. However, since immunotherapy was proclaimed as the breakthrough of the year in 2013, the focus on the stroma of pancreatic cancer has interestingly moved from activated fibroblasts to the immune compartment, trying to understand the immunosuppressive factors that play a part in the strong immune evasion that characterizes PDA. The PDA microenvironment is highly immunosuppressive and is basically composed of T regulatory cells (Tregs), tumor-associated macrophages (TAMs), and myeloid-derived suppressive cells (MDSCs), which block CD8+ T-cell duties in tumor recognition and clearance. Interestingly, preclinical data have highlighted the importance of this immune evasion as the source of resistance to single checkpoint immunotherapies and cancer vaccines and point at pathways that inhibit the immune attack as a key to solve the therapy puzzle. Here, we will discuss the molecular mechanisms involved in PDA immune escape as well as the state of the art of the PDA immunotherapy.


Tumor Biology ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 5281-5286 ◽  
Author(s):  
Xueyan Li ◽  
Xiaozhong Guo ◽  
Hongyu Li ◽  
Hao Lin ◽  
Yingwei Sun

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