{
  "abstract": "Background The immune system is posited to play a multifactorial role in cancer, including in the risk for development, growth, and progression of cancer. Moreover, understanding the immune system’s interactions with cancer has led to breakthroughs in treatments. However, uncertainties remain in the mechanistic potential of the immune system in the prevention and early detection of cancers, and whether these mechanisms are shared across cancers. To begin to address this gap we assessed the extent of shared immune drivers detectable in the circulation in at-risk individuals across the most common cancer types and explored if potential immune-related pathways exist that may be therapeutically beneficial.Methods Using the SomaScan Assay™®, approximately 7,000 proteins were assessed in ~15,000 plasma samples in a case-cohort subset of initially cancer-free participants in the European Prospective Investigation into Cancer study. Cox proportional hazards time-to-event univariate models of incident Breast, Lung, Prostate, and Colorectal cancer (n=949, 525, 945, 950 events respectively over 20-year follow-up) identified proteins significantly associated with each incident cancer type using a cutoff of FDR <0.1. Pathway and gene ontology enrichment analyses were conducted using DAVID to determine how the differentially expressed proteins function together in biological systems at the pathway and biological process level, respectively. Enriched pathway/process was considered significant for FDR <0.05.Results 3918, 2135, 1045 and 259 proteins passed the FDR 0.1 cutoff for association with incident Breast, Lung, Prostate and Colorectal cancer, respectively. Lung and breast cancer shared the highest proportion (72%) of overlapping proteins, whereas prostate and lung were the least overlapping cancer types sharing 34% proteins. KEGG pathway analysis of risk-associated proteins identified significant enrichment in immune-related pathways including chemokine signaling (breast and lung), complement and coagulation cascade (colorectal and lung), and Fc gamma R-mediated phagocytosis (lung).Thirty-four overlapping proteins were identified across all four cancers, with 18 (54%) being involved in at least one immune-related biological process (figure 1). Enrichment analysis indicated that the overlapping proteins converge on Wnt signaling.Conclusions We identified that blood-based proteomics detects significant immune involvement in the risk for the four most prevalent cancer types. High degrees of proteomic overlap between all cancers that converge on immune-related proteins and functions suggest shared immune interplays across cancers with Wnt signaling pathway as a common druggable or repurposable target. These results grant a better understanding of the common immune drivers across cancers and may aid in providing insights into preventative or early therapeutic targets.Ethics Approval The EPIC project was approved by the ethical review boards of the International Agency for Research on Cancer (Lyon, France) and from all local centres. Written informed consent was obtained from all participants.Abstract 39 Figure 1Overlapping risk proteins between common cancer types. The number of unique and common significant proteins (FDR <0.1) associated with future cancer risk",
  "authors": [
    {
      "affiliations": [
        "Standard BiTools, South San Francisco, CA, USA"
      ],
      "name": "Clare Paterson"
    },
    {
      "affiliations": [
        "Standard BiTools, South San Francisco, CA, USA"
      ],
      "name": "Jessica Chadwick"
    },
    {
      "affiliations": [
        "Standard BiTools, South San Francisco, CA, USA"
      ],
      "name": "Hannah R Biegel"
    },
    {
      "affiliations": [
        "Standard BiTools, South San Francisco, CA, USA"
      ],
      "name": "Sama Shrestha"
    },
    {
      "affiliations": [
        "Standard BiTools, South San Francisco, CA, USA"
      ],
      "name": "Stephen A Williams"
    }
  ],
  "title": "39 Identification of the common interplay between the immune system and multiple cancers using high-throughput plasma proteomics",
  "uid": "a9b6d297-6f86-5386-8663-5b73c5e087b0"
}