Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma

Zhang, Shi Rong; Yang, Lie; Wang, Wen Quan; Xu, Jin; Xu, Hua; Jin, Wei; Gao, He; Wu, Chun; Qi, Zi Hao; Li, Hao; Li, Shuo; Ni, Quanxing; Lei, Yu; Fu, De Liang

doi:10.1245/s10434-018-6941-4

Cited by 88 publications

(75 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Overall, these findings link PAD/citrullination-mediated formation of NETs with tumor growth and metastatic spreading of cancer cells potentially through ECM remodeling, surgical stress, hypoxia, increased fatty acid levels, or through physically binding metastasizing cells to establish colonies. In support of these basic studies results, tumor-infiltrating NETs predicted poor postsurgical survival of pancreatic cancer patients (73), emphasizing the clinical relevance of this phenomenon.…”

Section: Netsmentioning

confidence: 52%

Citrullination in Cancer

2019

View full text Add to dashboard Cite

Posttranslational modifications of proteins have been implicated in pathogenesis of numerous diseases. Arginine deimination (also known as citrullination) has a principal role in progression of rheumatoid arthritis through generation of autoantibodies and exacerbation of the inflammatory response. Recently, multiple research groups provided solid evidence of citrullination being in control of cancer progression; however, there is no comprehensive overview of these findings. This article summarizes and critically reviews the influence of citrul-lination on different aspects of tumor biology, including (i) regulation of apoptosis and differentiation, (ii) promoting EMT and metastasis, and (iii) potential use of citrullinated antigens for immunotherapy. In addition, (iv) the role of citrullination as a cancer biomarker and (v) implication of neutrophil extracellular traps in tumorigenesis are discussed. In summary, current findings testify to the significance of arginine deimination in tumor biology and thus more basic and translational studies are needed to further explore this topic. Brief Overview of PAD Biology and Function in Physiologic ConditionsPADs are a group of five Ca 2þ -dependent enzymes (PAD1-4 and PAD6), sharing 70% to 95% sequence homology and expressed in a wide range of tissues and organs ( Fig. 1D;

show abstract

Section: Netsmentioning

confidence: 52%

Citrullination in Cancer

2019

View full text Add to dashboard Cite

show abstract

“…In conclusion, with all recent publications linking elevated NET levels with the progression of several malignancies, such as breast (20) and colorectal (28) cancers, pancreatic ductal adenocarcinoma (29), ovarian metastasis (31), and -here -lung and gastroesophageal adenocarcinomas, it is interesting to see how successful NET-targeted therapies will be in clinical trials and how helpful NET-based biomarkers will be in predicting and prognosticating cancer progression and metastasis.…”

Section: Discussionmentioning

confidence: 97%

“…One group has shown that neutrophils isolated from colorectal cancer patients had increased NET production as compared with neutrophils isolated from age-matched healthy individuals following in vitro stimulation (28). Interestingly, NET levels were shown to be an independent prognostic factor in pancreatic ductal adenocarcinoma (29) and H3 Cittrulline (H3Cit), a good diagnostic and prognostic marker of cancer progression (30), showing the importance of NETs as biomarkers of cancer. Moreover, NETs were shown to facilitate ovarian cancer metastasis to the omentum (31), implicating NETs once again in cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

Primary tumors induce neutrophil extracellular traps with targetable metastasis-promoting effects

et al. 2019

View full text Add to dashboard Cite

“…To date, only one study has explored the ability of markers of NETs to predict a VTE event in pancreatic cancer patients [57], where an increase in these markers was associated with the occurrence of VTE. Additionally, Jin et al [59] observed that NETs markers predicted poor postsurgical survival of patients with PDAC. Furthermore, the incorporation of these markers with the standard TNM stating system refined the risk stratification and predicted survival in PDAC with improved accuracy.…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma

Oto

Navarro

Larsen

et al. 2020

IJMS

View full text Add to dashboard Cite

Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age- and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up- or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.

show abstract

Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma

Cited by 88 publications

References 39 publications

Citrullination in Cancer

Citrullination in Cancer

Primary tumors induce neutrophil extracellular traps with targetable metastasis-promoting effects

MicroRNAs and Neutrophil Activation Markers Predict Venous Thrombosis in Pancreatic Ductal Adenocarcinoma and Distal Extrahepatic Cholangiocarcinoma

Contact Info

Product

Resources

About