scholarly journals A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Validation Dataset ◽  
Healthy Controls ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Significant Difference ◽  
Rna Signature

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

scholarly journals The Screening and Early Detection of Pancreatic Cancer: Who, When, and How?

2020 ◽  
Vol 25 (2) ◽  
pp. 65-71
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Imaging Modality ◽  
Ductal Adenocarcinoma ◽  
Average Risk ◽  
Cystic Lesions ◽  
Low Prevalence ◽  
New Onset

More than 80% of patients with pancreatic ductal adenocarcinoma (PDA) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% resectable proportion to greater by early detection can be achieved, it will unequivocally lead to improved survival in this otherwise dismal disease. Although the goal of early detection of PDA is laudable, the relatively low prevalence PDA renders general population screening infeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define those subsets of individuals, such as familial kindred and patients with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to conduct surveillance in the atrisk individuals and the modalities (biomarkers and imaging) that will be used in the surveillance and diagnostic settings, respectively. Nonetheless, vast challenges still remain in terms of validated blood-based biomarkers, imaging modality, and when and how often the surveillance.

Can IL-2R Alpha be a Valuable Marker along with Ca 19–9 in the Diagnosis of Chronic Pancreatitis and Pancreatic Cancer?

2004 ◽  
Vol 19 (3) ◽  
pp. 196-202
Author(s):  
B. Kayhan ◽  
B. Kayhan ◽  
M. Akdoğ;an
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Interleukin 2 ◽  
Carbohydrate Antigen ◽  
Control Group ◽  
Serum Samples ◽  
Cancer Group ◽  
Abdominal Symptoms ◽  
Significant Difference ◽  
Inflammatory Processes

Background Pancreatic cancer is characterized initially by non-specific abdominal symptoms followed by rapid tumor progression. Although chronic pancreatitis is a benign disorder, it can be one of the causative factors of pancreatic cancer. The level of the tumor marker carbohydrate antigen 19–9 (CA 19–9) in pancreatic cancer does not correlate with the stage of the neoplasm. Soluble interleukin 2 receptor (sIL-2R) is a cytokine that shows increased levels during some inflammatory processes and malignant disorders. Aim Our aim in this study was to investigate whether sIL-2Rα levels can be used in association with CA 19–9 in the early diagnosis of pancreatic cancer and chronic pancreatitis. Patients Serum samples were obtained from the blood of 21 pancreatic cancer patients without distant metastasis who were deemed inoperable, 16 chronic pancreatitis patients and 20 normal volunteers. Results We did not find any significant differences in CA 19–9 levels between normal controls and patients with chronic pancreatitis. There was a significant difference in the levels between the control group and the pancreatic cancer group (p=0.003) and between patients with chronic pancreatitis and those with pancreatic cancer (p=0.004). Although there was no significant difference in sIL-2Rα levels between the control group and the patient groups, we found a slight correlation between sIL-2Rα and CA 19–9 levels in the pancreatic cancer group (p=0.003, r=0.623) and a more marked correlation in the chronic pancreatitis group (p<0.01, r=0.751). Conclusion According to our results, sIL-2Rα alone is not a good candidate marker in the diagnosis of pancreatic cancer; it can, however, be used in association with CA 19–9 for this purpose.

scholarly journals The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2353
Author(s):  
Nikhil Patel ◽  
Tatjana Petrinic ◽  
Michael Silva ◽  
Zahir Soonawalla ◽  
Srikanth Reddy ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Diagnostic Accuracy ◽  
Kras Mutation ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Cross Sectional ◽  
Specificity And Sensitivity ◽  
Variable Sensitivity

This meta-analysis aims to identify the diagnostic accuracy of mutations in the Kirsten Rat Sarcoma (KRAS) oncogene in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The survival of PDAC remains poor often due to the fact that disease is advanced at diagnosis. We analysed 22 studies, with a total of 2156 patients, to identify if the detection of KRAS mutations from pancreatic exocrine secretions yields sufficient specificity and sensitivity to detect patients with PDAC amongst healthy individuals. The majority of the studies were retrospective, samples were obtained endoscopically or surgically, and included comparator populations of patients with chronic pancreatitis and pre-malignant pancreatic lesions (PanIN) as well as healthy controls. We performed several analyses to identify the diagnostic accuracy for PDAC among these patient populations. Our results highlighted that the diagnostic accuracy of KRAS mutation for PDAC was of variable sensitivity and specificity when compared with PanINs and chronic pancreatitis, but had a higher specificity among healthy individuals. The sensitivity of this test must be improved to prevent missing early PDAC or PanINs. This could be achieved with rigorous prospective cohort studies, in which high-risk patients with normal cross-sectional imaging undergo surveillance following KRAS mutation testing.

Development of Pancreatic Cancer: Targets for Early Detection and Treatment

2016 ◽  
Vol 34 (5) ◽  
pp. 525-531 ◽  
Author(s):  
Markus M. Lerch ◽  
Julia Mayerle ◽  
Ujjwal Mahajan ◽  
Matthias Sendler ◽  
F. Ulrich Weiss ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Tyrosine Kinases ◽  
Histone Deacetylases ◽  
Hedgehog Signaling ◽  
Pharmaceutical Preparations ◽  
Chemotherapeutic Agents ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools

Background: Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer death worldwide and compared to other malignancies its share in cancer mortality is expected to rise further. This is due to a lack of sensitive diagnostic tools that would permit earlier detection in a potentially curable stage and the very slow progress in finding effective drug treatments for pancreatic cancer. Key Messages: Aside from genetic predispositions and environmental agents, chronic pancreatitis is by far the greatest risk factor for PDAC. It also shares several etiological factors with pancreatic cancer and represents its most challenging differential diagnosis. Biomarkers that can distinguish between chronic pancreatitis and PDAC may therefore be suitable for the latter's early detection. Moreover, targeting the natural history of chronic pancreatitis would be one approach to prevent PDAC. Targeting tumor-cell signaling directly by interfering with receptor tyrosine kinases has shown some efficacy, although the results in clinical trials were less encouraging than for other cancers. Other compounds developed have targeted the formation of extracellular matrix around the tumor, the proteolytic activity in the tumor environment, histone deacetylases, hedgehog signaling and heat shock proteins, but none has yet found its way into routine patient care. Attempts to individualize treatment according to the tumor's somatic mutation profile are novel but so far impractical. Conclusions: Progress in the treatment of pancreatic cancer has been exceedingly slow and mostly dependent on improved pharmaceutical preparations or combinations of established chemotherapeutic agents. The promise of major breakthroughs implied in targeting tumor signal transduction events has so far not materialized.

scholarly journals Characterizing the Skin and Gut Microbiome of Alopecia Areata Patients

2020 ◽  
Vol 4 (1) ◽  
pp. 23-30
Author(s):  
Margit Juhasz ◽  
Siwei Chen ◽  
Arash Khosrovi-Eghbal ◽  
Chloe Ekelem ◽  
Yessica Landaverde ◽  
...  
Keyword(s):  
Alopecia Areata ◽  
Gut Microbiome ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Microbial Composition ◽  
Future Directions ◽  
Fecal Microbiome ◽  
Autoimmune Attack ◽  
Significant Difference ◽  
Control Study

Background: Alopecia areata (AA) is caused by autoimmune attack of the hair follicle. The exact pathogenesis is unknown, but hypotheses include innate immunity imbalance, environmental exposures, genetic predisposition, and possibly the microbiome. The objective of this study was to characterize the skin and gut microbiome of AA patients, and compare microbial composition to healthy individuals. Methods: This was a pilot, case-control study. Scalp and fecal microbiome samples were collected from 25 AA patients, and 25 age, gender, and race-matched healthy controls in Southern California with no significant difference in demographic characteristics. After library preparation and identification of bacterial and fungal taxonomy, multivariant analysis was performed to compare AA and healthy microbiomes. Results: The AA scalp microbiome was significant for decreased Clostridia and Malasseziomycetes, and the gut microbiome was significant for decreased Bacteroidia and increased Bacilli (p<0.05) compared to healthy controls. Conclusions: The composition of the AA bacterial and fungal, scalp and gut microbiome is significantly different than healthy individuals. Future directions include using this data to characterize microbial changes associated with AA patient diet, relating to disease severity, and predicting disease progression, prognosis and/or therapeutic response.

scholarly journals Elevated Polyamines in Saliva of Pancreatic Cancer

2018 ◽  
Author(s):  
Yasutsugu Asai ◽  
Takao Itoi ◽  
Masahiro Sugimoto ◽  
Atsushi Sofuni ◽  
Takayoshi Tsuchiya ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pancreatic Cancer ◽  
Capillary Electrophoresis ◽  
Chronic Pancreatitis ◽  
Screening Test ◽  
High Accuracy ◽  
The Other ◽  
Non Invasive ◽  
Accurate Detection ◽  
Significant Difference

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n=39), chronic pancreatitis (CP, n=14) and controls (C, n=26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between PC and C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data showed the potential of saliva as a screening test for PC.

scholarly journals Screening of Pancreatic Cancer for Early Diagnosis

2021 ◽  
Vol 96 (2) ◽  
pp. 110-115
Author(s):  
Jae Hyuck Chang
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
General Population ◽  
Early Detection ◽  
Early Diagnosis ◽  
Average Risk ◽  
Cystic Lesions ◽  
Diagnostic Modalities ◽  
Low Prevalence ◽  
New Onset

Over 80% of patients with pancreatic ductal adenocarcinomas (PDAs) present with symptomatic, surgically unresectable disease. If a “stage shift” from the current 20% proportion of resectability to early detection could be achieved, this would greatly improve the survival of patients with this generally dismal disease. Although the goal of early detection is laudable, the relatively low prevalence of PDA renders general population screening unfeasible. To avoid the perils of overdiagnosis and to focus early detection efforts on individuals deemed to be at higher-than-average risk, we need to define such subsets of individuals, such as kindred of existing patients and those with precursor cystic lesions, chronic pancreatitis, and new-onset diabetes. The next step is to determine when and how often to monitor at-risk individuals and the diagnostic modalities that will be employed in the surveillance. Enormous challenges remain in terms of validated blood-based biomarkers, imaging modalities, and when and how often surveillance.

Novel nanobiosensor based protease biomarkers for early detection and prognosis of pancreatic cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16787-e16787
Author(s):  
Anup Kasi ◽  
James Kaiser Houghton ◽  
Anwaar Saeed ◽  
Stephen K. Williamson ◽  
Obdulia Covarrubias Zambrano ◽  
...  
Keyword(s):  
Early Detection ◽  
Small Sample ◽  
Cancer Center ◽  
Fluorescent Nanoparticles ◽  
Healthy Controls ◽  
Aberrant Expression ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Protease Expression

e16787 Background: Identifying novel biomarkers for early detection and prognosis would allow for improved survival outcomes in pancreatic cancer (PC). Arginase has been implicated in tumorigenesis through its production of L-ornithine. Its aberrant expression provides metabolites for tumor proliferation. Methods: In our study, 47 patients with metastatic PC, 29 with localized PC, and 50 healthy controls were enrolled at KU Cancer Center from 2000 to 2019. Overall survival (OS) was retrospectively assessed and correlated to serum protease levels at diagnosis. Protease expression was analyzed using nanobiosensors, which utilized fluorescent nanoparticles read by Spectra Scan to measure arginase, matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA), neutrophil elastase (NE), cathepsin B (CTSB), and cathepsin E (CTSE). Survival analysis was completed by Kaplan-Meier method. Results: Protease expression in localized vs. healthy cases was significant for (CTSB [p = 1.33E-10], MMP1 [p = 6.66E-21], MMP3 [p = 1.39E-13], MMP9 [p = 2.77E-08], NE [p = 0.00015], uPA [p = 2.55E-11]) and borderline significant for arginase [p = 0.05082]. Protease expression in metastatic vs. healthy cases was significant for (CTSB [p = 7.06E-06], MMP1 [p = 3.08E-12], MMP3 [p = 2.51E-14], MMP9 [p = 1.73E-08], NE [p = 0.01430], uPA [p = 0.00024]). Further, metastatic vs. localized cancer was significant for (arginase [p = 0.00034], CTSB [p = 0.00584], MMP1 [p = 2.03E-13], NE [p = 2.29E-10], and uPA [p = 6.58E-07]. Characteristics of 21 localized PC patients are illustrated in Table. Median OS was 25m in localized PC with low Arginase expression (mean < 215) vs 17.5m in high Arginase expression (p = 0.0477). Conclusions: Expression pattern of CTSB, MMP, NE, arginase, uPA proteases showed statistical significant difference for detection of localized PC vs metastatic PC vs healthy cases. In localized PC, lower arginase expression showed a statistically significant improvement in survival vs high arginase expression. Arginase expression was borderline significant for detection of localized PC vs healthy controls, likely due to small sample. Arginase as a potential biomarker for early detection and prognosis of PC warrants validation in a larger cohort. [Table: see text]

Pancreatic cancer in chronic pancreatitis; aetiology, incidence, and early detection

2010 ◽  
Vol 24 (3) ◽  
pp. 349-358 ◽  
Author(s):  
Sara Raimondi ◽  
Albert B. Lowenfels ◽  
Antonio M. Morselli-Labate ◽  
Patrick Maisonneuve ◽  
Raffaele Pezzilli
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection

scholarly journals Study on the Behavioural Assessment of the Dysexecutive Syndrome (BADS) performance in healthy individuals, Mild Cognitive Impairment and Alzheimer's disease: A preliminary study

2009 ◽  
Vol 3 (2) ◽  
pp. 101-107 ◽  
Author(s):  
Cristiane Garcia da Costa Armentano ◽  
Cláudia Sellitto Porto ◽  
Sonia Maria Dozzi Brucki ◽  
Ricardo Nitrini
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Rating Scale ◽  
Neuropsychiatric Symptoms ◽  
Inhibitory Response ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Significant Difference

Abstract Executive deficits as well as deficits in episodic memory characterize the initial phases of Alzheimer Disease (AD) and are clinically correlated to neuropsychiatric symptoms and functional loss. Patients with Mild Cognitive Impairment present more problems as to inhibitory response control, switching and cognitive flexibility. Objective: To compare performance on the BADS with performance on other executive functional tests among patients with mild Alzheimer's disease, Amnestic Mild Cognitive Impairment (aMCI) to performance of control individuals and to examine discriminative capacity of BADS among these groups. Methods: The BADS was performed by 35 healthy controls, 13 patients with aMCI, and 16 mild probable AD patients. Besides performing the BADS, subjects underwent neuropsychological evaluation which comprised: the Dementia Rating Scale (DRS), verbal fluency by phonemic categories (F.A.S) and Concentrated Attention Test (CA). Results: There were no differences among groups by educational level, but performance differed for age (p<0.01). No difference between healthy controls and aMCI patients was found on total scores or subitems of the BADS. A significant difference was observed between aMCI and AD patients (p<0.05) and between controls and AD patients (p<0.05) on total and standard scores. Conclusions: Performance on the BADS differed between healthy individuals and mild AD patients. The BADS proved to be a sensitive method for discriminating AD from aMCI.

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