Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review

Abstract

ObjectivesA systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken.Materials and MethodsA systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools.ResultsForty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response.ConclusionOur review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals.

Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines

“…In different cancer models, it was demonstrated that BRCA2 leads to accumulation of DNA breaks, and results in activation of p53, which promotes cell cycle arrest and activation of cell death [ 58 , 59 ]. Moreover, in cancer, BRCA2 inactivation leads to pro-inflammatory cytokines production, that is a determinant for cancer cell survival [ 60 ], and several studies have investigated the expression profile of various cytokines in patients with PDAC and Nuclear Factor kB (NF-κB) activation pathways that have also been shown to be involved in pancreatic cancer development [ 61 , 62 , 63 ]. Moreover, inhibiting NF-κB and its downstream targets, lead to the inhibition of proliferation, angiogenesis, and invasion as reported in the PDAC mouse model [ 64 ].…”

Leptin signaling and cancer chemoresistance: Perspectives

“…The concentration of six cytokines (IL-1β; IL-6, IL-8, VEGF, TGF, IL-10) were consistently reported to be increased in pancreatic ductal adenocarcinoma (PDAC) patients. These molecules were associated with the severity of PDAC ( i.e ., metastasis, tumor size, and advanced stage) that suggest these cytokines have prognostic biomarker for PC[127]. Additionally, IL-8/CXCR1 axis was associated with cancer stem cell properties in PC[128].…”

An impedimetric molecularly-imprinted biosensor for Interleukin-1β determination, prepared by in-situ electropolymerization on carbon screen-printed electrodes

“…Interleukin-1β (IL-1β), a pro-inflammatory cytokine is implicated in cancer cell proliferation [1], emerging now as a key mediator of carcinogenesis. Its involvement in the molecular pathways of cancer-related inflammation are being unravelled, especially in pancreatic [2], breast [3] and prostate cancers [4]. Monitoring this biomarker in point-of care may therefore contribute to follow-up the progress of cancer diseases.…”