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Plasma inflammatory cytokines and survival of pancreatic cancer patients.

ABSTRACT: OBJECTIVES:Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome. METHODS:We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for death were estimated using multivariate Cox proportional hazards models. RESULTS:Overall mortality was significantly increased in patients in the top quartile of CRP (HR?=?2.52, 95% CI: 1.82-3.49), IL-6 (HR?=?2.78, 95% CI: 2.03-3.81), sTNF-RII (HR?=?2.00, 95% CI: 1.46-2.72), and MIC-1 (HR?=?2.53, 95% CI: 1.83-3.50), compared to those in the bottom quartile (P-trend <0.0001 for all four comparisons). Furthermore, patients with higher circulating concentrations of all four cytokines had a median survival of 3.7 months; whereas, those with lower levels had a median survival of 19.2 months (HR?=?4.55, 95% CI: 2.87-7.20, P-trend <0.0001). CONCLUSION:Individual elevated plasma inflammatory cytokines are associated with significant and dramatic reductions in pancreatic cancer patient survival. Furthermore, we observed an independent combined effect of those cytokines on patient survival, suggesting that multiple inflammatory pathways are likely involved in PDAC progression. Future research efforts to target the inflammatory state using combination strategies in pancreatic cancer patients are warranted.

SUBMITTER: Babic A

PROVIDER: S-EPMC5915593 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Plasma inflammatory cytokines and survival of pancreatic cancer patients.

Babic A A Schnure N N Neupane N P NP Zaman M M MM Rifai N N Welch M W MW Brais L K LK Rubinson D A DA Morales-Oyarvide V V Yuan C C Zhang S S Poole E M EM Wolpin B M BM Kulke M H MH Barbie D A DA Wong K K Fuchs C S CS Ng K K

Clinical and translational gastroenterology 20180425 4

<h4>Objectives</h4>Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome.<h4>Methods</h4>We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), in ...[more]

PMID: 29691365

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Project description:To test whether or not the association between inflammation and pancreatic ductal adenocarcinoma (PC) is facilitated by host susceptibility, specifically by genetic polymorphisms in inflammation-related genes.Inflammation has been linked to PC. Reports have cited an increased expression of proinflammatory mediators, such as NF-?B and COX, in PC but not in normal adjacent tissue, suggesting a possible role in carcinogenesis. We sought to further understand the role that genetic variants in the NF-?B inflammatory pathway play in the development and progression of PC.We genotyped 1536 tag single nucleotide polymorphisms (SNPs) in 102 candidate genes of multiple inflammatory pathways in 1308 white patients with PC who were divided into 3 groups on the basis of the extent of disease: resected for cure (n = 400), locally advanced/unresected (n = 443), and metastatic (n = 465). Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards regression models. Statistical significance was set at less than 0.001 to control for multiple testing.Median age was 67 (28.0-91.0) years, and 57% were men. Median survival for each of the 3 groups (resected, locally advanced, and metastatic) was 23.7, 9.4, and 6.6 months, respectively (P < 0.0001). In the resected group, carriers of a minor allele for either rs3824872 (MAPK8IP1) or rs8064821 (SOCS3) were associated with a 10- and 6-month survival advantage compared with noncarriers in patients with resected disease, with an additional 2-year survival if both minor alleles were present. With locally advanced disease, SNP rs1124736 (IGF1R) was associated with improved survival if they had a copy of the G allele, hazard ratio of 0.57 (95% confidence interval: 0.42-0.77); P = 0.0002. In addition, 4 SNPs in patients with metastatic disease were found to be associated with worse survival and 2 associated with improved overall survival, but the differences in survival were deemed not clinically significant.SNPs in the inflammatory pathway genes MAPK8IP1 and SOCS3 were associated with increased overall survival in patients undergoing potentially curative resection and may be used in the future as markers to predict survival. Future research is needed to determine the functional relevance of these loci.

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Plasma inflammatory cytokines and survival of pancreatic cancer patients.

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Plasma inflammatory cytokines and survival of pancreatic cancer patients.

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