Development of biosensor for ovarian cancer biomarkers based on SPRI technique

• Grant number: 19/06803-4
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): January 01, 2020
• Effective date (End): December 31, 2020
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal researcher: Dayane Batista Tada
• Grantee: Erenildo Ferreira de Macedo
• Supervisor abroad: Yanxia Hou-Broutin
• Home Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Federal de São Paulo (UNIFESP). Campus São José dos Campos. São José dos Campos , SP, Brazil
• Research place: Commissariat à l'énergie atomique et aux énergies alternatives, Grenoble (CEA), France
• Associated to the scholarship: 16/07354-0 - Development of biosensor for Ovarian Cancer biomarkers based on surface plasmon resonance imaging, BP.DR

Abstract

Ovarian cancer is currently the most lethal gynecological cancer worldwide. This cancer usually has no symptoms leading to late diagnosis and poor survival of patients (overall fiveyear survival less than 40 %). In Brazil, ovarian cancer is the 8th most commonly diagnosed malignancy. In this way, it is essential to search for methods able to identify the disease at the early stages. Today one of the first tests performed in ovarian cancer investigation process is serum analysis for searching the presence of the protein CA-125 at increased levels. However, false-negative results are recurrent for this marker and in many cases, the increased levels of CA-125 are observed in patients only when the cancer is already advanced. Recently, several studies have addressed another possible marker for ovarian cancer, the protein mesothelin. Studies associated the overexpression of mesothelin to ovarian cancer but despite the large number of research in this topic, the analysis of this protein in the serum of patients with suspect of cancer is not yet part of medical protocol. Besides the serum levels, mesothelin is also used as a marker for immunohistology analysis of tumor tissue. Although ovarian cancer presented high levels of mesothelin, it may also be found in increased serum levels for other dysplasias not associated to cancer. Therefore, individual analysis of serum levels of CA-125 and mesothelin can not be considered as a diagnostic method of high specificity for ovarian cancer. However, recent studies have indicated that the interaction between CA-125 and mesothelin plays a key role in ovarian cancer metastasis to the peritoneum. Thus, the simultaneous overexpression of mesothelin and CA-125 may be specifically associated with ovarian cancer. For this reason, this project aims to develop a biosensor capable of detecting mesothelin and CA-125 simultaneously and at low concentrations. The biosensor is based on Surface Plasmon Resonance technique (SPR). The biosensor will be prepared with anti-mesothelin antibodies (MAb) 5B2 and / or (MAb) OV569 and anti-CA125 antibody OC-125. To increase the sensitivity of the biosensor it will be used nanoparticles (NPs) of gold functionalized with recombinant Federal University of São Paulo Institute of Science and Technology 2 proteins mesothelin and CA-125. These NPs will be mixed with the serum prior to analysis in the sensor. NPs are used as serum biomarkers catchers, thereby increasing the concentration of the analytes on the sensor surface. In addition to increased signal due to the increased concentration of the analyte, the NPs should increase the sensitivity of the sensor by coupling of electrons in the effect of plasmon resonance. Thus, it is expected to obtain a rapid method of diagnosis for early ovarian cancer and extend the applications of the SPR method with NPs to other types of diseases. (AU)