72 Spatial whole transcriptome profiling of the tumor microenvironment in prostate carcinomas

• DOI: 10.1136/jitc-2021-sitc2021.072
• Publication Date: 2021-11-09T15:01:43Z
• Authors: Naishitha Anaparthy; Valeria Giangarra; Sarah Taylor; Mesruh Turkekul; Stephen Williams; Paulius Mielinis; Caroline Gallant
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Background Despite years of studies and effort, the best strategies for treating prostate cancer minimizing complications treatment remain unanswered questions. This gap in knowledge is partially due to inability dissect complex heterogeneous tumor microenvironment (TME) immune compartment. Spatially resolved molecular profiling sections will enhance our understanding these complexities; However, it has been particularly challenging do spatial formalin-fixed paraffin-embedded (FFPE) tissues RNA degradation associated with this tissue-embedding method, which routinely used oncology workflows. The 10x Genomics Visium Spatial Gene Expression Solution FFPE tissue overcomes limitations, enabling gene expression analysis combined classical histology staining techniques such as Hematoxylin & Eosin (H&E) immunofluorescence. Methods We analyze resolve tumorigenic profiles normal adenocarcinoma samples. assay incorporates ~5,000 molecularly barcoded, spatially encoded capture probes spots over placed, imaged, permeabilized. Imaging sequencing data are processed together, resulting a transcriptional readout. Results profiled whole transcriptome normal, invasive adenocarcinoma, acinar cell carcinoma human tissues. Unsupervised clustering from enabled identification 2 different regions, had well defined distribution within Well known gland prostate-cancer markers were over-expressed corresponding healthy cancerous portions tissue, validating performance method. found that, while basal cells luminal organized, pattern lost samples, where greatly expanded region not colocalize cells. Moreover, T lymphocytes dispersed throughout section plasma B located peritumoral could impact prognosis. Conclusions opens new opportunities better TME can only help discover novel predictive biomarkers, but also enable identifying type specific drug targets.