Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma

Abstract

Background: Inflammatory mediators may have decisive roles at different stages of tumour development. Mediators within the pentraxin family may be used as strong biomarkers in prognosis of advanced pancreatic carcinoma patients.

Methods: Using pancreatic carcinoma cell lines and gene transfectant, we measured long pentraxin (PTX3) level in culture solution and carried out cellular migration assay in vitro. In vivo study of the treatment-naive patients with advanced pancreatic carcinoma assigned to undergo gemcitabine therapy was prospectively conducted to measure and investigate the role of plasma PTX3, C-reactive protein (CRP), and eight inflammatory mediators by using collected clinical data.

Results: Elevated PTX3 production was observed in several cell lines, and a direct relationship between migratory activity and PTX3 level was identified in vitro. High PTX3 level (117 days) was significantly less than that of patients with low PTX3 level (357 days, P<0.001). Multivariate analysis of the pancreatic carcinoma revealed a strong correlation between pentraxin family member expression and prognosis of pancreatic carcinoma. The relationship between PTX3 expression and the expression of other pro-inflammatory mediators indicated that PTX3 level is positively correlated with levels of CRP, interleukin-6, and macrophage-inhibitory factor.

Conclusion: Pentraxin family members, especially PTX3, may be used as promising biomarkers in the prognosis of pancreatic carcinoma patients.

Figure 1

(A) Pentraxin 3 production levels of supernatants used for culturing of pancreatic carcinoma cell lines. (B, C) Cell migration assay in the presence or absence of the indicated reagents. NT (non-treated), FBS, 20% in the lower chamber; VEGF, 50 ng ml⁻¹ in the lower chamber; PTX3, 50–100 ng ml⁻¹; CRP, 50–100 ng ml⁻¹. Statistical significance was evaluated by comparison with or without the presence of PTX3 and CRP.

Figure 2

(A) Pentraxin 3 production levels of supernatants used for culturing of PTX3 and NT-control transfectant of pancreatic carcinoma cell lines. (B) Cell migration assay using pancreatic carcinoma cell lines (AsPC-1 and PANC-1) transfected with pCMV6-entry PTX3 ORF in the presence or absence of the indicated reagents. NT (non-treated), FBS, 20% in the lower chamber; VEGF, 50 ng ml⁻¹ in the lower chamber; PTX3, 50–100 ng ml⁻¹; CRP, 50–100 ng ml⁻¹. Stable transformants were subjected to cell migration assay.

Figure 3

Kaplan–Meier curves for (A) progression-free survival according to blood-PTX3 level and (B) overall survival according to blood-PTX3 level. Cutoff points for PTX3 level were based on mean PTX3 level.