PWE-200 Metabolomic profiling in pancreatic cancer; in search of new biomarkers

Gut ◽  
2015 ◽  
Vol 64 (Suppl 1) ◽  
pp. A300.1-A300
Author(s):  
NP Ross ◽  
E Correa ◽  
N Rattray ◽  
D Hildebrand ◽  
Y Xu ◽  
...  
2021 ◽  
Vol 22 (5) ◽  
pp. 2655
Author(s):  
Randa G. Hanna-Sawires ◽  
Jorinde H. Schiphuis ◽  
Manfred Wuhrer ◽  
Hans F. A. Vasen ◽  
Monique E. van Leerdam ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.


Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1659 ◽  
Author(s):  
Verena Martini ◽  
Sylvia Timme-Bronsert ◽  
Stefan Fichtner-Feigl ◽  
Jens Hoeppner ◽  
Birte Kulemann

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.


PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93474 ◽  
Author(s):  
Joseph A. Rothwell ◽  
Yoann Fillâtre ◽  
Jean-François Martin ◽  
Bernard Lyan ◽  
Estelle Pujos-Guillot ◽  
...  

2012 ◽  
Vol 9 (8) ◽  
pp. 435-444 ◽  
Author(s):  
Eithne Costello ◽  
William Greenhalf ◽  
John P. Neoptolemos

2020 ◽  
Vol 21 (17) ◽  
pp. 6193
Author(s):  
Ala Litman-Zawadzka ◽  
Marta Łukaszewicz-Zając ◽  
Mariusz Gryko ◽  
Agnieszka Kulczyńska-Przybik ◽  
Bogusław Kędra ◽  
...  

Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing. Objectives: The aim of our study was to compare the utility of CXCR2 and CXCR4 in the diagnosis and prediction of PC with classical tumor marker (carcinoembryonic antigen, CEA) and marker of inflammation–C-reactive protein (CRP). Patients and Methods: The study comprised 64 subjects — 32 PC patients and 32 healthy volunteers. Serum concentrations of tested proteins were analysed using immunological methods. Results: Serum CXCR2 and CXCR4 concentrations, similarly to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Moreover, concentrations of CXCR4 were significantly correlated with CXCR2 and CRP levels, while CRP concentrations were correlated with CXCR2 and CEA levels. The diagnostic sensitivity and the predictive value for negative (PV−ve) results for CXCR4 were similar to those of CEA and higher than those of CXCR2 and CRP, while the area under the ROC curve (AUC) for CXCR4 was the highest among all tested proteins (CXCR2, CEA, CRP). Moreover, serum CXCR2 was found to be a significant predictor of PC risk. Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk.


Gut ◽  
2015 ◽  
Vol 64 (Suppl 1) ◽  
pp. A299.2-A300
Author(s):  
NP Ross ◽  
ES Correa ◽  
NJ Rattray ◽  
DR Hildebrand ◽  
DK Trivedi ◽  
...  

2012 ◽  
Vol 310 ◽  
pp. 44-51 ◽  
Author(s):  
Prabhjit Kaur ◽  
Kathryn Sheikh ◽  
Alexander Kirilyuk ◽  
Ksenia Kirilyuk ◽  
Rajbir Singh ◽  
...  

2007 ◽  
Vol 5 (10) ◽  
pp. 1034-1041 ◽  
Author(s):  
David E. Misek ◽  
Tasneem H. Patwa ◽  
David M. Lubman ◽  
Diane M. Simeone

Major advances in cancer control will be greatly aided by early detection for diagnosing and treating cancer in its preinvasive state before metastasis. Unfortunately, for pancreatic ductal adenocarcinoma (PDAC), which is the fourth leading cause of cancer-related death in the United States, effective early detection and screening are currently not available and tumors are typically diagnosed at a late stage, frequently after metastasis. Partly because of low sensitivity/specificity, existing biomarkers such as CA19-9 are not adequate as early detection markers of pancreatic cancer. Thus, a great need exists for new biomarkers for pancreatic cancer. This article focuses on recent developments in the identification of new serum protein biomarkers that are useful in the early detection of PDAC.


2021 ◽  
Author(s):  
Nicholas D. Nguyen ◽  
Meifang Yu ◽  
Vinit Y. Reddy ◽  
Ariana C. Acevedo-Diaz ◽  
Enzo C. Mesarick ◽  
...  

Mitochondria are dynamic organelles that constantly alter their shape through the recruitment of specialized proteins, like mitofusin-2 (Mfn2) and dynamin-related protein 1 (Drp1). Mfn2 induces the fusion of nearby mitochondria, while Drp1 mediates mitochondrial fission. We previously found that the genetic or pharmacological activation of mitochondrial fusion was tumor suppressive against pancreatic ductal adenocarcinoma (PDAC) in several model systems. The mechanisms of how these different inducers of mitochondrial fusion reduce pancreatic cancer growth are still unknown. Here, we characterized and compared the metabolic reprogramming of these three independent methods of inducing mitochondrial fusion in KPC cell: overexpression of Mfn2, genetic editing of Drp1, or treatment with leflunomide. We identified significantly altered metabolites via robust, orthogonal statistical analyses and found that mitochondrial fusion consistently produces alterations in the metabolism of amino acids. Our unbiased methodology revealed that metabolic perturbations were similar across all these methods of inducing mitochondrial fusion, proposing a common pathway for metabolic targeting with other drugs.


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