scholarly journals A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Anna S. Gerdtsson ◽  
Núria Malats ◽  
Anna Säll ◽  
Francisco X. Real ◽  
Miquel Porta ◽  
...  

Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91–100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis.

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3515
Author(s):  
Christelle de la Fouchardière ◽  
Mustapha Adham ◽  
Anne-Marie Marion-Audibert ◽  
Antoine Duclos ◽  
Claude Darcha ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) remains a major public health challenge, and faces disparities and delays in the diagnosis and access to care. Our purposes were to describe the medical path of PDAC patients in the real-life setting and evaluate the overall survival at 1 year. We used the national hospital discharge summaries database system to analyze the management of patients with newly diagnosed PDAC over the year 2016 in Auvergne-Rhône-Alpes region (AuRA) (France). A total of 1872 patients met inclusion criteria corresponding to an incidence of 22.6 per 100,000 person-year. Within the follow-up period, 353 (18.9%) were operated with a curative intent, 743 (39.7%) underwent chemo- and/or radiotherapy, and 776 (41.4%) did not receive any of these treatments. Less than half of patients were operated in a high-volume center, defined by more than 20 PDAC resections performed annually, mainly university hospitals. The 1-year survival rate was 47% in the overall population. This study highlights that a significant number of patients with PDAC are still operated in low-volume centers or do not receive any specific oncological treatment. A detailed analysis of the medical pathways is necessary in order to identify the medical and territorial determinants and their impact on the patient’s outcome.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Imteyaz Ahmad Khan ◽  
Safoora Rashid ◽  
Nidhi Singh ◽  
Sumaira Rashid ◽  
Vishwajeet Singh ◽  
...  

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.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Sophia Chikhladze ◽  
Ann-Kathrin Lederer ◽  
Lampros Kousoulas ◽  
Marilena Reinmuth ◽  
Olivia Sick ◽  
...  

Abstract Background The recommendation for postoperative chemotherapy in pancreatic ductal adenocarcinoma (PDAC) is based on prospective randomized trials. However, patients included in clinical trials do not often reflect the overall patient population treated in clinical practice. Materials and methods A retrospective review of all patients undergoing pancreas resection for PDAC between 2001 and 2013 was performed. Follow-up data from oncologists, general practitioners, or hospital patient files were available for 92% of patients. Results A total of 251 patients were included in our analysis. Chemotherapy was recommended for 223 patients, but 86 patients did not follow the recommendation. The application of the recommended chemotherapy, consisting of 6 cycles of gemcitabine, was only applied to 45 patients. Forty patients received the recommended number of cycles with dose reduction or prolonged intervals between cycles, and adjuvant chemotherapy was terminated prior to the intended completion of all 6 cycles in 54 patients. Survival of patients after adjuvant chemotherapy was increased compared to that of patients without chemotherapy (with recurrence 25.6 vs. 14.3 months, p = 0.001, and without recurrence 27.4 vs. 14.3 months, p <  0.001). Terminating chemotherapy prior to completion (p = 0.009) as well as a lower number of chemotherapy cycles (p = 0.026) was associated with a decreased survival. Conclusion Adjuvant chemotherapy improves overall and disease-free survival after curative pancreatic resection, but only a small fraction of patients completes the recommended 6 cycles of adjuvant chemotherapy. Our data indicates that performance status of patients after pancreas resections for PDAC requires not only highly biologically active but also well-tolerated adjuvant chemotherapy regimens.


Oncotarget ◽  
2018 ◽  
Vol 9 (61) ◽  
pp. 31861-31876 ◽  
Author(s):  
Gemma Bruera ◽  
Silvia Massacese ◽  
Stefania Candria ◽  
Antonio Galvano ◽  
Rosa Manetta ◽  
...  

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16761-e16761
Author(s):  
Yaolin Xu ◽  
Dansong WANG ◽  
Tiantao Kuang ◽  
Wenchuan Wu ◽  
Xuefeng Xu ◽  
...  

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]


2016 ◽  
Vol 22 (4) ◽  
pp. 348-359 ◽  
Author(s):  
Sandra Ríos Peces ◽  
Caridad Díaz Navarro ◽  
Cristina Márquez López ◽  
Octavio Caba ◽  
Cristina Jiménez-Luna ◽  
...  

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.


2021 ◽  
Vol 22 (12) ◽  
pp. 6501
Author(s):  
Violeta Morcuende-Ventura ◽  
Sonia Hermoso-Durán ◽  
Natalia Abian-Franco ◽  
Roberto Pazo-Cid ◽  
Jorge L. Ojeda ◽  
...  

(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.


Sign in / Sign up

Export Citation Format

Share Document