A Serum-Induced Transcriptome and Serum Cytokine Signature Obtained at Diagnosis Correlates with the Development of Early Pancreatic Ductal Adenocarcinoma Metastasis.

Abstract

Despite the accessibility of blood, identification of systemic biomarkers associated with cancer progression has been especially challenging. The aim of this study was to determine a difference in baseline serum immune signatures in patients that experienced early pancreatic ductal adenocarcinoma (PDAC) metastasis compared with patients that did not. We hypothesized that immune mediators would differ in the baseline serum of these patient cohorts. To test this hypothesis, novel approaches of systemic immune analysis were performed. A serum-induced transcriptional assay was used to identify transcriptome signatures. To enable an understanding of the transcriptome data in a global sense, a transcriptome index was calculated for each patient taking into consideration the relationship of up- and downregulated transcripts. For each patient, serum cytokine concentrations were also analyzed globally as a cytokine index (CI). A transcriptome signature of innate type I IFN inflammation was identified in patients that experienced early metastatic progression. Patients without early metastatic progression had a baseline transcriptome signature of TGFβ/IL10-regulated acute inflammation. The transcriptome index was greater in patients with early metastasis. There was a significant difference in the CI in patients with and without early metastatic progression. The association of serum-induced transcriptional signatures with PDAC metastasis is a novel finding. Global assessment of serum cytokine concentrations as a CI is a novel approach to assess systemic cancer immunity. These systemic indices can be assessed in combination with tumor markers to further define subsets of PDAC that will provide insight into effective treatment, progression, and outcome.