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      Potential biomarkers for early detection of pancreatic ductal adenocarcinoma

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          Abstract

          Pancreatic cancer has the highest mortality amongst all major organ cancers. Early detection is key to reduce deaths related to pancreatic cancer. However, early detection has been challenged by the lack of non-invasive biomarkers with enough sensitivity and specificity to allow for screening. The gold standard is still carbohydrate antigen (CA 19-9), against which all new biomarkers must be evaluated. In this paper, we describe recent progress in the development of new pancreatic cancer biomarkers, focusing on proteins, metabolites, and genetic and epigenetic biomarkers. Although several promising biomarkers have been identified, they are all derived from retrospective studies and additional prospective studies are needed to confirm their clinical validity.

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          Glypican-1 identifies cancer exosomes and detects early pancreatic cancer.

          A. Melo, Linda Luecke, Christoph Kahlert … (2015)
          Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes. GPC1(+) circulating exosomes (crExos) were monitored and isolated using flow cytometry from the serum of patients and mice with cancer. GPC1(+) crExos were detected in the serum of patients with pancreatic cancer with absolute specificity and sensitivity, distinguishing healthy subjects and patients with a benign pancreatic disease from patients with early- and late-stage pancreatic cancer. Levels of GPC1(+) crExos correlate with tumour burden and the survival of pre- and post-surgical patients. GPC1(+) crExos from patients and from mice with spontaneous pancreatic tumours carry specific KRAS mutations, and reliably detect pancreatic intraepithelial lesions in mice despite negative signals by magnetic resonance imaging. GPC1(+) crExos may serve as a potential non-invasive diagnostic and screening tool to detect early stages of pancreatic cancer to facilitate possible curative surgical therapy.
          Article 0 comments Cited 691 times – based on 0 reviews     Review now
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            Detection and localization of surgically resectable cancers with a multi-analyte blood test

            Nickolas Papadopoulos, Robert E. Schoen, Randall Brand … (2018)
            Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was > 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.
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              Distant Metastasis Occurs Late during the Genetic Evolution of Pancreatic Cancer

              Shinichi Yachida, Siân Jones, Ivana Bozic … (2010)
              Summary Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated 1 2 , is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemo- or radiation therapy 3 . Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.
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                Author and article information

                Contributors
                R. Andersson:
                ORCID: http://orcid.org/0000-0003-0778-8630
                roland.andersson@med.lu.se
                Journal
                Journal ID (nlm-ta): Clin Transl Oncol
                Journal ID (iso-abbrev): Clin Transl Oncol
                Title: Clinical & Translational Oncology
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 1699-048X
                ISSN (Electronic): 1699-3055
                Publication date (Electronic): 23 May 2020
                Publication date PMC-release: 23 May 2020
                Publication date (Print): 2020
                Volume: 22
                Issue: 12
                Pages: 2170-2174
                Affiliations
                Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
                Author information
                http://orcid.org/0000-0003-0778-8630
                Article
                Publisher ID: 2372
                DOI: 10.1007/s12094-020-02372-0
                PMC ID: 7578134
                PubMed ID: 32447642
                SO-VID: 3beb8d1f-8898-473a-972b-85670fdb86d6
                Copyright © © The Author(s) 2020
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 16 January 2020
                Date accepted : 1 May 2020
                Categories
                Subject: Review Article
                Custom metadata
                issue-copyright-statement © Federación de Sociedades Españolas de Oncología (FESEO) 2020

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pancreatic cancer,early detection,biomarkers,sensitivity,specificity
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pancreatic cancer, early detection, biomarkers, sensitivity, specificity

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