scholarly journals Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 732
Author(s):  
Annie He Ren ◽  
Ioannis Prassas ◽  
Antoninus Soosaipillai ◽  
Stephanie Jarvi ◽  
Steven Gallinger ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Serum Protein ◽  
Biomarker Discovery ◽  
Tumor Burden ◽  
Antibody Microarray ◽  
Cancer Heterogeneity ◽  
Post Surgery ◽  
Single Target ◽  
Recent Developments ◽  
Concentration Changes

Background: To account for cancer heterogeneity, we previously introduced the concept of “personalized” tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer. Methods: We applied the Quantibody® Human Kiloplex Array to simultaneously measure 1,000 proteins in sera obtained pre- and post-surgically from five pancreatic cancer patients. We expected that proteins which decreased post-surgery may correlate to tumor burden. Sera from two healthy individuals, split into two aliquots each, were used as controls. To validate the multiplexed results, we used single-target ELISA assays to measure the proteins with the largest serum concentration changes after surgery in sera collected pre- and post-surgically from the previous five patients and 10 additional patients. Results: The multiplexed array revealed nine proteins with more than two-fold post-surgical decrease in at least two of five patients. However, validation using single ELISAs showed that only two proteins tested displayed more than two-fold post-surgical decrease in one of the five original patients. In the independent cohort, six of the proteins tested showed at least a two-fold decrease post-surgery in at least one patient. Conclusions: Our study found that the Quantibody® Human Kiloplex Array results could not be reliably replicated with individual ELISA assays and most hits would likely represent false positives if applied to biomarker discovery. These findings suggest that data from novel, high-throughput proteomic platforms need stringent validation to avoid false discoveries.

scholarly journals Investigating a novel multiplex proteomics technology for detection of changes in serum protein concentrations that may correlate to tumor burden

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 732 ◽  
Author(s):  
Annie He Ren ◽  
Ioannis Prassas ◽  
Antoninus Soosaipillai ◽  
Stephanie Jarvi ◽  
Steven Gallinger ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Serum Protein ◽  
Biomarker Discovery ◽  
Tumor Burden ◽  
Antibody Microarray ◽  
Cancer Heterogeneity ◽  
Post Surgery ◽  
Single Target ◽  
Recent Developments ◽  
Concentration Changes

Background: To account for cancer heterogeneity, we previously introduced the concept of “personalized” tumor markers, which are biomarkers that are informative in subsets of patients or even a single patient. Recent developments in various multiplex protein technologies create excitement for the discovery of markers of tumor burden in individual patients, but the reliability of the technologies remains to be tested for this purpose. Here, we sought to explore the potential of a novel proteomics platform, which utilizes a multiplexed antibody microarray, to detect changes in serum protein concentration that may correlate to tumor burden in pancreatic cancer. Methods: We applied the Quantibody® Human Kiloplex Array to simultaneously measure 1,000 proteins in sera obtained pre- and post-surgically from five pancreatic cancer patients. We expected that proteins which decreased post-surgery may correlate to tumor burden. Sera from two healthy individuals, split into two aliquots each, were used as controls. To validate the multiplexed results, we used single-target ELISA assays to measure the proteins with the largest serum concentration changes after surgery in sera collected pre- and post-surgically from the previous five patients and 10 additional patients. Results: The multiplexed array revealed nine proteins with more than two-fold post-surgical decrease in at least two of five patients. However, validation using single ELISAs showed that only two proteins tested displayed more than two-fold post-surgical decrease in one of the five original patients. In the independent cohort, six of the proteins tested showed at least a two-fold decrease post-surgery in at least one patient. Conclusions: Our study found that the Quantibody® Human Kiloplex Array results could not be reliably replicated with individual ELISA assays and most hits would likely represent false positives if applied to biomarker discovery. These findings suggest that data from novel, high-throughput proteomic platforms need stringent validation to avoid false discoveries.

Detection of pancreatic cancer using antibody microarray-based serum protein profiling

PROTEOMICS ◽  
2008 ◽  
Vol 8 (11) ◽  
pp. 2211-2219 ◽  
Author(s):  
Johan Ingvarsson ◽  
Christer Wingren ◽  
Anders Carlsson ◽  
Peter Ellmark ◽  
Britta Wahren ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Serum Protein ◽  
Protein Profiling ◽  
Antibody Microarray

scholarly journals Current State of “Omics” Biomarkers in Pancreatic Cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 127 ◽  
Author(s):  
Beste Turanli ◽  
Esra Yildirim ◽  
Gizem Gulfidan ◽  
Kazim Yalcin Arga ◽  
Raghu Sinha
Keyword(s):  
Pancreatic Cancer ◽  
Personalized Medicine ◽  
Biomarker Discovery ◽  
Survival Rates ◽  
Postoperative Recurrence ◽  
Molecular Biomarkers ◽  
Background Information ◽  
Current State ◽  
Pancreatic Cancer Screening ◽  
The Future

Pancreatic cancer is one of the most fatal malignancies and the seventh leading cause of cancer-related deaths related to late diagnosis, poor survival rates, and high incidence of metastasis. Unfortunately, pancreatic cancer is predicted to become the third leading cause of cancer deaths in the future. Therefore, diagnosis at the early stages of pancreatic cancer for initial diagnosis or postoperative recurrence is a great challenge, as well as predicting prognosis precisely in the context of biomarker discovery. From the personalized medicine perspective, the lack of molecular biomarkers for patient selection confines tailored therapy options, including selecting drugs and their doses or even diet. Currently, there is no standardized pancreatic cancer screening strategy using molecular biomarkers, but CA19-9 is the most well known marker for the detection of pancreatic cancer. In contrast, recent innovations in high-throughput techniques have enabled the discovery of specific biomarkers of cancers using genomics, transcriptomics, proteomics, metabolomics, glycomics, and metagenomics. Panels combining CA19-9 with other novel biomarkers from different “omics” levels might represent an ideal strategy for the early detection of pancreatic cancer. The systems biology approach may shed a light on biomarker identification of pancreatic cancer by integrating multi-omics approaches. In this review, we provide background information on the current state of pancreatic cancer biomarkers from multi-omics stages. Furthermore, we conclude this review on how multi-omics data may reveal new biomarkers to be used for personalized medicine in the future.

scholarly journals Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3631
Author(s):  
Krystal Villalobos-Ayala ◽  
Ivannie Ortiz Rivera ◽  
Ciara Alvarez ◽  
Kazim Husain ◽  
DeVon DeLoach ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Responses ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Tumor Burden ◽  
Sh2 Domain ◽  
Src Homology 2 ◽  
Src Homology ◽  
And Function ◽  
Deficient Mice

Pancreatic cancer (PC) has an extremely poor prognosis due to the expansion of immunosuppressive myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in the inflammatory tumor microenvironment (TME), which halts the recruitment of effector immune cells and renders immunotherapy ineffective. Thus, the identification of new molecular targets that can modulate the immunosuppressive TME is warranted for PC intervention. Src Homology-2 (SH2) domain-containing Inositol 5′-Phosphatase-1 (SHIP-1) is a lipid signaling protein and a regulator of myeloid cell development and function. Herein, we used the bioflavonoid apigenin (API) to reduce inflammation in different PC models. Wild type mice harboring heterotopic or orthotopic PC were treated with API, which induced SHIP-1 expression, reduced inflammatory tumor-derived factors (TDF), increased the proportion of tumoricidal macrophages and enhanced anti-tumor immune responses, resulting in a reduction in tumor burden compared to vehicle-treated PC mice. In contrast, SHIP-1-deficient mice exhibited an increased tumor burden and displayed augmented proportions of pro-tumor macrophages. These results provide further support for the importance of SHIP-1 expression in promoting pro-tumor macrophage development in the pancreatic TME. Our findings suggest that agents augmenting SHIP-1 expression may provide novel therapeutic options for the treatment of PC.

scholarly journals Recent developments in diagnosis of pancreatic cancer

BMJ ◽  
2004 ◽  
Vol 329 (7467) ◽  
pp. 668-673 ◽  
Author(s):  
Arjun S Takhar ◽  
Ponni Palaniappan ◽  
Rajpal Dhingsa ◽  
Dileep N Lobo
Keyword(s):  
Pancreatic Cancer ◽  
Recent Developments

scholarly journals A simple serum depletion method for proteomics analysis

BioTechniques ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 148-151
Author(s):  
Alexandre Zougman ◽  
John P Wilson ◽  
Rosamonde E Banks
Keyword(s):  
Sample Preparation ◽  
Serum Protein ◽  
Body Fluid ◽  
Biomarker Discovery ◽  
The Body ◽  
Protein Digestion ◽  
Proteomics Analysis ◽  
Serum Proteome ◽  
Serum Fractions

Serum is the body fluid most often used in biomarker discovery. Albumin, the most abundant serum protein, contributes approximately 50% of the serum protein content, with an additional dozen abundant proteins dominating the rest of the serum proteome. To profile this challenging protein mixture by proteomics, the abundant proteins must be depleted to allow for detection of the low-abundant proteins, the primary biomarker targets. Current serum depletion approaches for proteomics are costly and relatively complex to couple with protein digestion. We demonstrate a simple, affordable serum depletion methodology that, within a few minutes of processing, results in two captured serum fractions – albumin-depleted and albumin-rich – which are digested in situ. We believe our method is a useful addition to the biomarker sample preparation toolbox.

Proteomic analysis for early detection of ovarian cancer: A realistic approach?

2003 ◽  
Vol 13 (Suppl 2) ◽  
pp. 133-139 ◽  
Author(s):  
E. V. Stevens ◽  
L. A. Liotta ◽  
E. C. Kohn
Keyword(s):  
Ovarian Cancer ◽  
Early Detection ◽  
Serum Protein ◽  
Mass Spectroscopy ◽  
Biomarker Discovery ◽  
Protein Pattern ◽  
Protein Biomarkers ◽  
Promising Tool ◽  
Chip Technology ◽  
Stage Disease

Ovarian cancer is a multifaceted disease wherein most women are diagnosed with advanced stage disease. One of the most imperative issues in ovarian cancer is early detection. Biomarkers that allow cancer detection at stage I, a time when the disease is amenable to surgical and chemotherapeutic cure in over 90% of patients, can dramatically alter the horizon for women with this disease. Recent developments in mass spectroscopy and protein chip technology coupled with bioinformatics have been applied to biomarker discovery. The complexity of the proteome is a rich resource from which the patterns can be gleaned; the pattern rather than its component parts is the diagnostic. Serum is a key source of putative protein biomarkers, and, by its nature, can reflect organ-confined events. Pioneering use of mass spectroscopy coupled with bioinformatics has been demonstrated as being capable of distinguishing serum protein pattern signatures of ovarian cancer in patients with early- and late-stage disease. This is a sensitive, precise, and promising tool for which further validation is needed to confirm that ovarian cancer serum protein signature patterns can be a robust biomarker approach for ovarian cancer diagnosis, yielding improved patient outcome and reducing the death and suffering from ovarian cancer.

Methodology of Pancreatic Juice Collection from the Duodenum for Biomarker Discovery and Early detection of Pancreatic Cancer

Pancreatology ◽  
2020 ◽  
Vol 20 ◽  
pp. S146-S147
Author(s):  
I. Levink ◽  
K. Nesteruk ◽  
D. Visser ◽  
C. Fernandes ◽  
M. Jansen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Detection ◽  
Pancreatic Juice ◽  
Biomarker Discovery
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