Abstract 6280: Exploring the dynamics of plasma proteins and their effect on outcomes in patients with bladder and lung cancer

Abstract The immune system’s state and composition affects the outcome for patients with cancer. Here we investigated the dynamics of immune-related proteins in relation to treatment or recurrence in muscle-invasive bladder cancer (MIBC) and non-small cell lung cancer (NSCLC). Using the Olink Proteomics Explore 1536 panel, we measured the level of 1536 proteins across multiple time points (2-6) for 25 patients with MIBC. Additionally, we obtained public data from the TRACERx cohort, where 151 patients with NSCLC had been profiled using the Olink Explore 3072 panel, measuring 3072 proteins at two time points. We investigated the association of the protein levels with immune-related parameters (T cell receptor diversity and relative T cell fraction) and patient outcome using mixed effects models. Significant proteins were further investigated in pathway enrichment analyses using both the Hallmark and Reactome pathways, and selected proteins were investigated individually. Cox Proportional Hazard Ratio was used to evaluate the proteins’ association with survival. We found 70 proteins that were significantly associated with metastatic disease in MIBC with enrichment of proteins in immune-related pathways. Seven proteins were associated with T cell receptor diversity and 19 were associated with the T cell fraction, which were enriched in proliferation pathways. In NSCLC we found 66 proteins that were associated with the T cell receptor diversity, and these were enriched among immune regulation pathways and pathways related to NOTCH signaling and cell-cell communication. Only six proteins were associated with the T cell fraction in the patients with NSCLC, and these were enriched in immune-related pathways. In the NSCLC cohort, we found 400 proteins that were negatively associated with overall survival and 86 proteins that were associated with improved overall survival. Among the 400 proteins, we observed an enrichment of proteins related to the innate immune system. In conclusion, we find proteins that are associated with outcome or immune-related measures in both cohorts, and combined these proteins are enriched across pathways associated with the immune system, proliferation, or cell-cell communication, all pathways that have a role in cancer development. Citation Format: Randi Istrup Juul, Asbjørn Kjær, Nanna Kristjánsdóttir, Iver Nordentoft, Lars Dyrskjøt, Nicolai J. Birkbak. Exploring the dynamics of plasma proteins and their effect on outcomes in patients with bladder and lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6280.