Serum biomarker panel diagnostics in pancreatic ductal adenocarcinoma: the clinical utility of soluble interleukins, IFN-γ, TNF-α and PD-1/PD-L1 in comparison to established serum tumor markers

Abstract

Purpose Novel biomarkers to better predict outcome and select the best therapeutic strategy for the individual patient are necessary for pancreatic ductal adenocarcinoma (PDAC). Methods Using a panel assay, multiple biomarkers (IFN-γ, IL-10, IL-6, IL-8, TNF-α, CEA, CA 19–9, CYFRA 21–1, HE4, PD-1 and PD-L1 levels) were measured in serum samples of 162 patients with resected, locally advanced and metastatic PDAC in this retrospective single-center study. Optimal cut-off values to differentiate prognostic subgroups with significantly different overall survival (OS) were determined by receiver operator characteristics and Youden Index analysis. Marker levels were assessed before the start of chemotherapy and correlated with OS by univariate and multivariate Cox analysis. Results Median OS for resected patients was 28.2 months, for locally advanced patients 17.9 months and for patients with metastatic disease 8.6 months. CYFRA 21–1 and IL-8 discriminated metastatic from locally advanced patients best (AUC 0.85 and AUC 0.81, respectively). In univariate analyses, multiple markers showed prognostic relevance in the various subgroups. However, multivariate Cox models comprised only CYFRA 21–1 in the resected group (HR 1.37, p = 0.015), IL-10 in locally advanced PDAC (HR 10.01, p = 0.014), as well as CYFRA 21–1 and CA 19–9 in metastatic PDAC (p = 0.008 and p = 0.010) as an independent prognostic marker for overall survival. Conclusion IL-10 levels may have independent prognostic value in locally advanced PDAC, whereas CYFRA 21–1 levels are prognostic after PDAC surgery. CYFRA 21–1 and IL-8 have been identified to best discriminate metastatic from locally advanced patients.

Precision Oncology in Pancreatic Cancer: Experiences and Challenges of the CCCMunichLMU Molecular Tumor Board

“…Furthermore, we compared the group of 88 patients with synchronous metastatic disease to a historic cohort of 90 patients with pancreatic cancer with synchronous metastatic disease who had been diagnosed at our comprehensive cancer center between December 2010 and August 2017. The baseline characteristics of this group including also some patients with metachronous metastatic disease have been reported previously [ 18 ]. The proportion of male and female patients was similar in both cohorts (MTB cohort 63.3% male vs comparative cohort 65.9% male).…”

Analysis of the mechanisms regulating soluble PD-1 production and function in human NK cells

“…Importantly, soluble checkpoints are also considered novel therapeutic targets and potential biomarkers. Indeed, high levels of both sPD-1 and sPD-L1 forms have been detected in plasma/serum of different cancer patients, compared to healthy donors (HDs), and have been associated with tumor prognosis, therapeutic response and overall survival (OS) (32)(33)(34)(35)(36)(37). Although, several studies demonstrated the pivotal role of sPD-1 in controlling cytotoxic T cells anti-cancer function, there is a lack of knowledge on the role of sPD-1 toward human NK cells.…”