Abstract 1041: Spatial concordance between genome and proteome in oncology: A systematic review

Abstract

Abstract We recently reported that spatial transcriptome data can be used to spatially detect copy number alterations (Erickson et al., Nature, 2022). Given that copy-number alterations may also be reflected by altered protein expression in human cancers, we sought to determine what the empirical concordance of the spatial proteome and genome in human cancer samples. We performed a systematic review of Immunohistochemistry (IHC) & Fluorescence/Chromogenic In-Situ Hybridization (FISH/CISH) across human cancers. We performed a PUBMED query for records up to April 1st, 2023, yielding 9,294 records. Our inclusion criteria included human sample studies that performed both IHC and FISH/CISH against the same target, with a minimum of two samples. We excluded case reports, RNA ISH- and non-human studies, studies without IHC/ISH performed on the same target, and articles not in English or inaccessible. We screened 9,294 PUBMED article abstracts using the AS Review active learning model (van de Schoot et al., 2021), and used a pre-defined threshold of 5 % consecutive irrelevant abstracts to stop screening. A total of 1,309 abstracts were manually excluded using the AS Review, directing the active learning model to automatically exclude 3,413 abstracts out of the original 9,294. Of the 4,572 articles assessed for full-article screening, 1,167 were excluded for being out of scope, 303 for access issues, 227 for language incompatibility, and 236 for imprecise information, primarily due to non-representative samples or incorrect gene/protein target identification. Ultimately, out of 2,413 articles assessed for eligibility, 2,294 did not meet inclusion criteria, leaving 119 studies for our analysis. From these articles, we manually extracted kappa values for analysis and visualization in R. We identified articles from 19 different cancers with the majority studying Breast Cancer, Non-Small Cell Lung Cancer, Gastric Cancer, and Mesothelioma. We observed high Cohen’s Kappa values in Breast Cancer (median = 0.76), Non-Small Cell Lung Cancer (median = 0.91) and Mucinous Ovarian Carcinoma (median = 0.93). We identified studies from 14 different genes with majority being HER2, ALK and MYC. We observed high Cohen’s Kappa values in HER2 (median = 0.80), ALK (median = 0.80), ROS1 (median = 0.95) and MDM2 (median = 0.72). Our preliminary analysis indicates significant heterogeneity between tumor types for protein expression and copy-number alterations. To our knowledge, there are no previously reported systematic reviews that have empirically assessed the spatial concordance of proteome and genome, in human cancer samples. The authors often reported IHC/FISH results at patient, or section level, potentially introducing selection bias by not accounting for intra-tumoral heterogeneity at single-cell resolution. Future efforts are needed to spatially resolve gene-copy number and protein expression at single-cell resolution. Citation Format: Laura K. Sysivirta, Franziska Niemeyer, Veera Kurki, Inkalilja Pirinen, Laura Savolainen, Ceren Seref-Vujaklilja, Andrew Erickson. Spatial concordance between genome and proteome in oncology: A systematic review [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1041.