Abstract 4632: Spatial whole transcriptome analysis of differential expression for biomarker discovery in colorectal cancer

Abstract

Abstract Background: Colorectal cancer (CRC) is one of the leading causes of cancer death, which is frequently caused by genetic or epigenetic changes. The study of tumor microenvironment (TME) profiling may provide a better knowledge of spatial gene expression patterns of known CRC markers, visualize the cell composition and localization, and serve to aid the understanding of the mechanisms of tumor formation. BioChain Institute, Inc. is currently investigating the TME profiling of CRC through tissue-wide, whole transcriptome analysis for the ability to discover potential therapeutic targets. Methods: BioChain’s formalin-fixed paraffin-embedded (FFPE) tissue samples from 3 primary colon adenocarcinoma tumors (PT), and their matched adjacent normal tissues (PN), were used to investigate the TME. The images of Hematoxylin and Eosin (H&E)-stained tissue sections were annotated by our pathologist. The spatial whole transcriptome was analyzed using 10x Genomics Visium Spatial Gene Expression for FFPE. This assay provided about 5,000 spatially barcoded spots with mRNA-binding oligonucleotides to capture the gene expression. The integration of the imaging and sequencing data enabled a spatially resolved transcriptome of CRC heterogeneity. Results: The annotations of both PT and PN tissue samples were found to be correlated with the spatial gene expression clustering. With the overlaying of total gene counts for each spot on the H&E-stained tissue image, about 16,000-17,000 genes were detected in each sample. The median of ~5,500 and ~1,600 genes per spot were expressed in PT and PN samples respectively. The study of gene expression levels revealed the overexpression of several well-known CRC markers (APOE, SCD, IGFBP3, TIMP1, SPARC) and the down-regulation of numerous markers (DES, CA1, KLF4) in PT samples significantly. Conclusion: Our spatial analysis results provide insight into tumor heterogeneity, spatial organization of cells within the TME and biomarker identification. BioChain is in a unique position to facilitate researchers with a plethora of oncologic and other diseased tissue types, as well as the spatial whole transcriptome analysis. Our study enables the understanding of the TME, discovery of potential diagnostic and prognostic targets, especially for the development of personalized therapy. Citation Format: Elim Cheung, Vidyodhaya Sundaram, Baowen Zhang, Lutong Zhang, Tong Lu. Spatial whole transcriptome analysis of differential expression for biomarker discovery in colorectal cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4632.