Abstract

AbstractGrowth arrest‐specific 6 (GAS6) protein plays a key role in processes related to proliferation, inflammation, angiogenesis, and atherosclerotic plaque formation. In addition, it has been reported that plasma levels of GAS6 are related to cancer prognosis and other relevant pathologies, such as heart failure or sepsis. We report here the first electrochemical immunoplatform for the determination of GAS6, which has demonstrated to be competitive with other available methodologies in terms of cost, simplicity, and decentralized application. The developed immunoplatform involves a sandwich immunoassay using magnetic microparticles (MBs) and uses amperometric detection at disposable screen‐printed carbon electrodes (SPCEs). The MBs were modified with an antibody specific to GAS6 for its selective capture, which is further recognized by a biotinylated secondary antibody subsequently labeled with a streptavidin‐horseradish peroxidase (Strep‐HRP) conjugate. The electrochemical detection was carried out using the hydroquinone (HQ)/H2O2 system. The developed bioplatform exhibits a great selectivity and low limit of detection (27 pg/mL) that allowed the determination of the GAS6 circulating level in plasma samples from patients suffering heart failure (HF) and diagnosed with pancreatic ductal adenocarcinoma (PDAC), as well as the determination of the target protein in raw secretomes of human colorectal cancer cell lines.

Highlights

  • Biomarkers can be used for a better understanding of fundamental biological processes, providing information on what is happening in a cell or an organism at a given moment and serving as early warnings for health monitoring.Growth arrest-specific 6 (GAS6) protein has been proposed as an important factor in some complex pathological processes.[1]

  • The developed immunosensor was applied to the determination of the GAS6 circulating level in plasma from patients of heart failure (HF) or pancreatic cancer, and in secretomes of human colorectal cancer (CRC) cell lines

  • The plasma samples from control individuals and patients diagnosed with HF and pancreatic ductal adenocarcinoma (PDAC) were provided by the Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) and Hospital del Mar Medical Research Institute (IMIM), respectively, with the corresponding ethical permissions (IDIBAPS 2009/4729; IMIM 2020/9067/I), and the informed consent from all the involved individuals

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Summary

Introduction

Biomarkers can be used for a better understanding of fundamental biological processes, providing information on what is happening in a cell or an organism at a given moment and serving as early warnings for health monitoring.Growth arrest-specific 6 (GAS6) protein has been proposed as an important factor in some complex pathological processes.[1]. Biomarkers can be used for a better understanding of fundamental biological processes, providing information on what is happening in a cell or an organism at a given moment and serving as early warnings for health monitoring. GAS6 exerts its effects by binding TYRO3, Axl, and Mer receptor tyrosine-kinases (TAM family), showing the highest affinity for Axl.[2] It is mainly expressed in the lungs, heart, kidneys, intestine, bone marrow, vascular smooth muscle cells, monocytes and, at very low levels, in the liver,[3] and the GAS6 plasma concentration is much lower than that other VKDPs.[4] It has been reported that GAS6 plays key roles in several biological processes including proliferation, migration, differentiation, and adhesion, leukocyte sequestration, platelet aggregation and hematopoiesis, apoptosis, and phagocytosis, and that it is generally associated with conditions of injury, inflammation, and repair.[3,5]

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