Abstract 4897: Personalized cell surface target identification from pan-cancer RNA-seq and proteomics profiling of tumors

Abstract

Abstract In its third phase, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) program collected pan-cancer data from 1,069 patients profiling the transcriptome, proteome, and phospho-proteome of tumors and adjacent tissues from ten cancer types. To identify potential immunotherapeutic candidates from this CPTAC cohort, we searched for cell-surface proteins that are highly expressed in tumor subtypes compared to their expression in normal tissues and cell types from ARCHS4 and the Genotype-Tissue Expression (GTEx) resources. For each cancer type, tumor samples were first clustered into subtypes based on RNA-seq data, and then cell surface targets were prioritized for each cluster. These targets were subsequently confirmed for high protein expression in the tumor subtypes. Tumor samples were also processed by their classification into immune subtypes to identify targets specific to hot (CD8+/IFNG+) and cold (CD8-/IFNG-) tumors of each cancer type. For each cancer type, the computational pipeline identified ~30 cell surface proteins that are highly expressed in the tumor and lowly expressed across tissues and cell types in both the ARCHS4 and GTEx backgrounds. Many of these targets are also robustly differentially expressed at the proteome level. Several targets were shared across tumor types, including VTCN1 and TMPRSS4. Altogether, this rational approach to identify potential targets demonstrates a pipeline that can be applied for personalized cancer diagnosis and therapeutic development. Citation Format: Giacomo B. Marino, Eden Z. Deng, Daniel J.B. Clarke, Weiping Ma, Pei Wang, Adam C. Resnick, Avi Ma'ayan. Personalized cell surface target identification from pan-cancer RNA-seq and proteomics profiling of tumors [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 4897.