Design and Characterization of a Dual-Protein Strategy for an Early-Stage Assay of Ovarian Cancer Biomarker Lysophosphatidic Acid

Biosensors (Basel). 2024 Jun 2;14(6):287. doi: 10.3390/bios14060287.

Abstract

The overall 5-year survival rate of ovarian cancer (OC) is generally low as the disease is often diagnosed at an advanced stage of progression. To save lives, OC must be identified in its early stages when treatment is most effective. Early-stage OC causes the upregulation of lysophosphatidic acid (LPA), making the molecule a promising biomarker for early-stage detection. An LPA assay can additionally stage the disease since LPA levels increase with OC progression. This work presents two methods that demonstrate the prospective application for detecting LPA: the electromagnetic piezoelectric acoustic sensor (EMPAS) and a chemiluminescence-based iron oxide nanoparticle (IONP) approach. Both methods incorporate the protein complex gelsolin-actin, which enables testing for detection of the biomarker as the binding of LPA to the complex results in the separation of gelsolin from actin. The EMPAS was characterized with contact angle goniometry and atomic force microscopy, while gelsolin-actin-functionalized IONPs were characterized with transmission electron microscopy and Fourier transform infrared spectroscopy. In addition to characterization, LPA detection was demonstrated as a proof-of-concept in Milli-Q water, buffer, or human serum, highlighting various LPA assays that can be developed for the early-stage detection of OC.

Keywords: EMPAS; actin; antifouling linker; atomic force microscopy; chemiluminescence; gelsolin; lysophosphatidic acid; nanoparticles; ovarian cancer.

MeSH terms

  • Actins
  • Biomarkers, Tumor*
  • Biosensing Techniques
  • Early Detection of Cancer
  • Female
  • Gelsolin
  • Humans
  • Lysophospholipids*
  • Ovarian Neoplasms* / diagnosis

Substances

  • Lysophospholipids
  • lysophosphatidic acid
  • Biomarkers, Tumor
  • Gelsolin
  • Actins

Grants and funding

A portion of this research was conducted at the Department of Chemistry, University of Toronto. This work was funded under the European Union’s Horizon 2020 research and innovation program through the Marie Skłodowska-Curie grant agreement No 101007299 and by Science Agency VEGA, project No. 1/0445/23 (to T.H.). Support for this work was also provided by the Canadian Institutes of Health Research (CIHR Grant, PJT 180421 to MT).