Electrochemical Imaging of Biomarkers for Oral Cancer Staging

Abstract

Each year, approximately 450,000 new cases are reported with oral or oropharyngeal cancer worldwide. Despite their high incidence, oral cancers are often neglected at the first stage, resulting in cancer metastasis with high mortality rate, especially for men. Conventional methods for diagnosis of oral cancer rely on the visual inspection and biopsy. However, it may lead to misdiagnosis or delayed diagnosis because of insufficient information. Therefore, it is important to develop a novel tool for the detection of oral cancer at an initial stage itself.Electrochemical screening methods have shown to be very promising for the rapid, sensitive, and cost-effective detection of oral cancer biomarkers.1 To enhance the resolution of the electrochemical imaging, we employ the concept of image fusion, with the image obtained by scanning electrochemical microscopy (SECM) and optical microscopy. Through the prediction of the presence of biomarkers in tissue area, the fused image can provide a more accurate description of the biomarker distribution of the oral cancer slices. For the purpose of investigating the distribution of IL-6 protein, a biomarker of oral cancer, in different cancer stages, we use SECM to image tissue sections and fused it with H&E stain images obtained by optical microscope. SECM is a scanning probe technique that is composed of three electrode system and soft probe can scan closely over a sample surface. The primary antibody and secondary antibody labeled with horse radish peroxidase (HRP) were applied to reveal the locations of IL-6 on the samples. Then, the cancer sections were immersed in electrolytes containing FcMeOH and H2O2. The FcMeOH+ ions were generated from the catalytic reaction of HRP, and hence, the Faradaic current signals from the reduction of FcMeOH+ can be recorded through the scanning of SECM probe. Due to the fusion of SECM with H&E stain, IL-6 distribution patterns in cancers with different stages can be analyzed precisely. We discovered that in stage III of oral cancer, the IL-6 expression level is the highest as compared to the normal tissue and cancer tissue at earlier stages. 1. T.-E. Lin, Y.-J. Lu, C.-L. Sun, H. Pick, J. P. Chen, A. Lesch, H. H. Girault, Angew. Chem. Int. Ed. 2017, 56, 16498-162. T.-E. Lin, C.-L. Chen, Y.-C. Huang, H.-H. Chung, C.-W. Lin, K.-C. Chen, Y.-J. Peng, S.-T. Ding, M.-Y. Wang, T.-L. Shen, C.-C. Hsu Anal. Chim. Acta. 2019.