Poster Presentation 36th Lorne Cancer Conference 2024

Developing novel nucleic acid based detection system for immunostaining of cancer tissues (#140)

Jasmine Catague 1 2 , Shweta Patel 3 , Satendra Jaysawal 1 2 , Rajindra Napit 1 2 , Haben Melke 1 2 , Rocky Chowdhury 1 2 , Lingxue Kong 4 , Wei Duan 1 2
  1. School of Medicine, Deakin University, Geelong, Victoria, Australia
  2. Institute of Mental and Physical Health and Clinical Translation (IMPACT), , Deakin University, Geelong, Victoria, Australia
  3. Icon Cancer Centre, Adelaide, South Australia, Australia
  4. Institute for Frontier Materials, Deakin University, Geelong, Victoria, Australia

As of 2020, cancer is responsible for almost 10 million deaths making it one of the leading causes of death worldwide[1].  For most cancers, late detection is the primary reason for this high mortality rates. Thus, improving early diagnosis of cancer and monitoring of metastasis will lead to improved patient’s quality of life. The use of routine immunohistochemistry (IHC) in clinical pathology has been an integral element of histopathological examination of many cancers. IHC detects cell-specific biomarkers that can be used to differentially diagnose cell origin which is useful for diagnostic, prognostic, and personalised treatment for better patient treatment strategies[2,3]. Different tumour biomarkers such as EpCAM, HER2 and EGFR can be used as a target to develop novel aptamer molecular probes. EpCAM is overexpressed in 70-90% of carcinomas so it can be used as a clinically relevant target cancer biomarker[4].

However, the caveats of the currently used commercially available antibodies for IHC including cross-reactivity and lack of specificity relate to ~42% of diagnostic inconsistencies [5]. To overcome this problem, alternative nucleic-acid based system using aptamer as a molecular probe and DNAzyme as a reporter molecule can be used to replace the current protein-based antibody-HRP system. Aptamers are chemical antibodies with a relatively smaller size which has faster in vivo diffusion, less steric hindrance and better tumour penetration for epitope targeting in IHC application [4].

Optimising the current aptamer molecular probe against EpCAM to be attached to a sensitive peroxidase-mimicking DNAzyme as a reporter molecule will allow for a more accurate and sensitive cancer biomarker detection using IHC. This novel nucleic acid-based approach would address the limitations of the current IHC technique, leading to faster and more accurate cancer diagnosis and improved patient care.