Abstract 3812: Spatial whole transcriptome profiling of the tumor microenvironment in FFPE prostate carcinoma using the Visium platform
Authors: Williams Stephen Richardson , Giangarra Valeria , Anaparthy Naishitha , Turkekul Mesruh , Mielinis Paulius , Gallant Caroline , Weisenfeld Neil I. , Taylor Sarah E. , Chell James 
Published: June 2022

Despite years of prostate cancer-related research, balancing the risk of treatment-derived complications with tumor progression risk remains a challenge. The inability to dissect heterogeneous tumor microenvironments (TME) and immune compartments partly contribute to this knowledge gap. Spatially resolved molecular tumor profiling can enhance our understanding of these complexities and bring us closer to personalized treatment; however, deploying such methods in oncology workflows is challenging as the prevalent tissue preservation technique of formalin fixation and paraffin embedding (FFPE) leads to RNA degradation.We used tissue-wide whole transcriptome analysis with 10x Genomics Visium Spatial Gene Expression Solution for FFPE tissue to resolve the tumor microenvironment of two prostate cancer samples. This assay incorporates ~5,000 molecularly barcoded, spatially encoded capture probes in spots over which the tissue is placed, imaged, and permeabilized. Imaging and sequencing data are processed together for spatially resolved transcriptional readout. We analyzed, and resolved whole transcriptome tumorigenic profiles in sections of normal, stage III invasive adenocarcinoma, and stage IV acinar cell carcinoma FFPE human prostate tissues. Computational clustering of the whole-transcriptome data automatically identified spatial gene expression patterns that aligned well with pathologist annotations. Well known prostate gland and prostate cancer markers were over-expressed in the corresponding healthy and cancerous tumor tissue, validating this method. The data showed that basal cells and luminal cells are spatially organized in healthy tissue while this pattern is lost in tumor samples as the luminal cells encroach the invasive carcinoma region and do not colocalize with basal cells. Moreover, T lymphocytes are dispersed throughout the whole tissue in the adenocarcinoma, while plasma B cells are in the peritumoral region which could impact prognosis. Using computational methods to infer CNV profiles, we identified aneuploidy regions and specific loci that may be driving the underlying genomic profile of the cancerous regions. We demonstrated that spatial whole transcriptome analysis can successfully resolve FFPE prostate samples. Whole-transcriptome data can rapidly confirm known patterns of cell type and tumor region-specific gene expression while giving a better understanding of the TME for drug target identification or biomarker discovery that may lead to patient-tailored therapies and improved patient stratification.

Citation Format: Stephen Richardson Williams, Valeria Giangarra, Naishitha Anaparthy, Mesruh Turkekul, Paulius Mielinis, Caroline Gallant, Neil I. Weisenfeld, Sarah E. Taylor, James Chell. Spatial whole transcriptome profiling of the tumor microenvironment in FFPE prostate carcinoma using the Visium platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3812.