Nanomaterials augmented LDI-TOF-MS for pancreatic ductal adenocarcinoma diagnosis and classification.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16761-e16761
Author(s):  
Yaolin Xu ◽  
Dansong WANG ◽  
Tiantao Kuang ◽  
Wenchuan Wu ◽  
Xuefeng Xu ◽  
...  
Keyword(s):  
Cancer Screening ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Low Cost ◽  
Stage Iv ◽  
Mass Range ◽  
Ductal Adenocarcinoma ◽  
Healthy Controls ◽  
Serum Samples ◽  
Screening And Surveillance ◽  
Tof Ms

e16761 Background: Pancreatic ductal adenocarcinoma (PAAD) is one type of cancer with poor prognosis. Although CA 19-9 was the most common serological marker for cancer screening and surveillance after treatment, there are still unignorable limitations, including low sensitivity, possible false-negatives/positives owing to confounding conditions. Reliable non-invasive diagnostics is in urgent need. As PAAD is increasingly considered as a metabolic disorder, serum metabolite profiling is becoming critical to reveal important cancer-related bioinformation. This work proposes a novel LDI-TOF-MS technique for PAAD screening and diagnosis. Methods: An LDI-TOF-MS platform was established for cancer screening. All mass spectrum was collected within a mass range of 100 to 1,100 Da, while the spectra were manually examined using the FlexAnalysis 3.4 software (Bruker Daltonics, Bremen, Germany). In a typical process, 0.5 uL of serum samples were spotted on a polished steel target plate MTP 384 and air-dried followed by another 1 uL of GNS or SiNW nanomaterials. The spectra were then acquired in the reflection positive mode with smartbeam-II laser at 355 nm with laser frequency of 1,000 Hz. A random walk of 25 shots at raster spot and 20 different spots were measured for each individual sample, therefore, 500 satisfactory shots were obtained. Results: By taking advantage of 3D nanostructures and machine learning, we applied proposed approach to 94 patients with PAAD, as well as 203 healthy controls (Table). The results demonstrated an average sensitivity of 99% and a specificity over 98% in detecting cancers. 11 of 94 PAAD patients (11.70%) were CA 19-9 negative (CA19-9 < 37U/ml, stage I n = 2, stage II n = 7, stage III n = 1 and stage IV n = 1). LDI-TOF-MS recognized almost all CA 19-9-negative PAAD. The sensitivity and specificity were obviously superior to CA 19-9 in PAAD: only 1 of 94 PAAD (1.06%) were misclassified as healthy controls. In contrast, CA19-9 positive and CA 19-9 negative PAADs were not readily distinguished by this method. Therefore, this method was independent of tumor markers. Conclusions: Result suggested strong potential of proposed technique as a low-cost, superior precision, and high-throughput procedure for PAAD diagnosis and beyond. [Table: see text]

scholarly journals Panel of serum miRNAs as potential non-invasive biomarkers for pancreatic ductal adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Early Stage ◽  
Ductal Adenocarcinoma ◽  
Next Generation ◽  
Serum Samples ◽  
Tissue Samples ◽  
Non Invasive ◽  
Specific Symptoms ◽  
Generation Sequencing

AbstractEarly-stage diagnosis of pancreatic ductal adenocarcinoma (PDAC) is difficult due to non-specific symptoms. Circulating miRNAs in body fluids have been emerging as potential non-invasive biomarkers for diagnosis of many cancers. Thus, this study aimed to assess a panel of miRNAs for their ability to differentiate PDAC from chronic pancreatitis (CP), a benign inflammatory condition of the pancreas. Next-generation sequencing was performed to identify miRNAs present in 60 FFPE tissue samples (27 PDAC, 23 CP and 10 normal pancreatic tissues). Four up-regulated miRNAs (miR-215-5p, miR-122-5p, miR-192-5p, and miR-181a-2-3p) and four down-regulated miRNAs (miR-30b-5p, miR-216b-5p, miR-320b, and miR-214-5p) in PDAC compared to CP were selected based on next-generation sequencing results. The levels of these 8 differentially expressed miRNAs were measured by qRT-PCR in 125 serum samples (50 PDAC, 50 CP, and 25 healthy controls (HC)). The results showed significant upregulation of miR-215-5p, miR-122-5p, and miR-192-5p in PDAC serum samples. In contrast, levels of miR-30b-5p and miR-320b were significantly lower in PDAC as compared to CP and HC. ROC analysis showed that these 5 miRNAs can distinguish PDAC from both CP and HC. Hence, this panel can serve as a non-invasive biomarker for the early detection of PDAC.

scholarly journals Referral patterns and predictors of survival for stage IV pancreatic ductal adenocarcinoma

2018 ◽  
Vol 29 ◽  
pp. viii574
Author(s):  
A.E. Suo ◽  
P.A. Tang ◽  
D. Tilley ◽  
W.Y. Cheung ◽  
R. Lee-Ying
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Stage Iv ◽  
Ductal Adenocarcinoma ◽  
Referral Patterns

scholarly journals Extracellular Vesicle-Based Detection of Pancreatic Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yesim Verel-Yilmaz ◽  
Juan Pablo Fernández ◽  
Agnes Schäfer ◽  
Sheila Nevermann ◽  
Lena Cook ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Roc Curves ◽  
Serum Levels ◽  
Extracellular Vesicle ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Healthy Controls ◽  
Precursor Lesions ◽  
Healthy Individuals ◽  
Serum Samples

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.

scholarly journals Untargeted LC-HRMS-Based Metabolomics for Searching New Biomarkers of Pancreatic Ductal Adenocarcinoma: A Pilot Study

2016 ◽  
Vol 22 (4) ◽  
pp. 348-359 ◽  
Author(s):  
Sandra Ríos Peces ◽  
Caridad Díaz Navarro ◽  
Cristina Márquez López ◽  
Octavio Caba ◽  
Cristina Jiménez-Luna ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
High Resolution ◽  
Pancreatic Ductal Adenocarcinoma ◽  
High Resolution Mass Spectrometry ◽  
Ductal Adenocarcinoma ◽  
Serum Samples ◽  
High Resolution Mass ◽  
Dismal Prognosis ◽  
Resolution Mass

Pancreatic ductal adenocarcinoma is one of the most lethal tumors since it is usually detected at an advanced stage in which surgery and/or current chemotherapy have limited efficacy. The lack of sensitive and specific markers for diagnosis leads to a dismal prognosis. The purpose of this study is to identify metabolites in serum of pancreatic ductal adenocarcinoma patients that could be used as diagnostic biomarkers of this pathology. We used liquid chromatography–high-resolution mass spectrometry for a nontargeted metabolomics approach with serum samples from 28 individuals, including 16 patients with pancreatic ductal adenocarcinoma and 12 healthy controls. Multivariate statistical analysis, which included principal component analysis and partial least squares, revealed clear separation between the patient and control groups analyzed by liquid chromatography–high-resolution mass spectrometry using a nontargeted metabolomics approach. The metabolic analysis showed significantly lower levels of phospholipids in the serum from patients with pancreatic ductal adenocarcinoma compared with serum from controls. Our results suggest that the liquid chromatography–high-resolution mass spectrometry–based metabolomics approach provides a potent and promising tool for the diagnosis of pancreatic ductal adenocarcinoma patients using the specific metabolites identified as novel biomarkers that could be used for an earlier detection and treatment of these patients.

scholarly journals Preoperative Biomarker Panel, Including Fibrinogen and FVIII, Improves Diagnostic Accuracy for Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 24 (8) ◽  
pp. 1267-1275 ◽  
Author(s):  
Nora Mattila ◽  
Hanna Seppänen ◽  
Harri Mustonen ◽  
Beata Przybyla ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Diagnostic Accuracy ◽  
Factor Viii ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Neoadjuvant Treatment ◽  
Stage Iv ◽  
University Hospital ◽  
Ductal Adenocarcinoma ◽  
Characteristic Analysis ◽  
Coagulation Activity

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer often diagnosed late. Earlier detection is urgently needed. Pancreatic ductal adenocarcinoma is known to associate with increased coagulation activity. We studied whether preoperative coagulation biomarkers are useful in distinguishing PDAC from a benign tumor, intraductal papillary mucinous neoplasm (IPMN) in this observational study. We analyzed standard clinical and coagulation variables in patients operated during 2010 and 2015 at Helsinki University Hospital. Pancreatic ductal adenocarcinoma with preoperative coagulation variables available and no neoadjuvant treatment or other active cancer was observed in 80 patients (stage I-III in 67 and IV in 13) and IPMN in 18 patients. Fibrinogen, factor VIII (FVIII), carbohydrate antigen (CA) 19-9, albumin, alkaline phosphatase, and conjugated bilirubin were higher in both stages I to III and IV PDAC compared to IPMN ( P < .05). Factor VIII was highest in stage IV ( P < .05). Combining these variables in a panel increased sensitivity and specificity for PDAC. In receiver operating characteristic analysis, the area under the curve (95% confidence interval) was 0.95 (0.90-1.00) for the panel, compared to 0.80 (0.71-0.88) for CA 19-9 alone ( P < .01). In conclusion, PDAC was associated with increased fibrinogen and FVIII. Combining these coagulation biomarkers with CA 19-9, albumin, and alkaline phosphatase improves diagnostic accuracy.

scholarly journals Fluorescence Liquid Biopsy for Cancer Detection Is Improved by Using Cationic Dendronized Hyperbranched Polymer

2021 ◽  
Vol 22 (12) ◽  
pp. 6501
Author(s):  
Violeta Morcuende-Ventura ◽  
Sonia Hermoso-Durán ◽  
Natalia Abian-Franco ◽  
Roberto Pazo-Cid ◽  
Jorge L. Ojeda ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Classification Performance ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Diagnostic Model ◽  
Healthy Individuals ◽  
Serum Samples

(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.

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