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Clinical significance of elevated serum soluble CD40 ligand levels as a diagnostic and prognostic tumor marker for pancreatic ductal adenocarcinoma

Authors
 Hye Won Chung  ;  Jong-Baeck Lim 
Citation
 JOURNAL OF TRANSLATIONAL MEDICINE, Vol.12 : 102, 2014 
Journal Title
 JOURNAL OF TRANSLATIONAL MEDICINE 
Issue Date
2014
MeSH
Adenocarcinoma/blood* ; Adenocarcinoma/diagnosis ; Adenocarcinoma/physiopathology ; Biomarkers, Tumor/blood* ; CD40 Ligand/blood* ; Carcinoma, Pancreatic Ductal/blood* ; Carcinoma, Pancreatic Ductal/diagnosis ; Carcinoma, Pancreatic Ductal/physiopathology ; Humans ; Pancreatic Neoplasms/blood* ; Pancreatic Neoplasms/diagnosis ; Pancreatic Neoplasms/physiopathology ; Prognosis
Keywords
Biomarker ; Diagnostic ; Pancreatic cancer ; Prognostic ; Soluble CD40 ligand
Abstract
BACKGROUND: CD40-CD40 ligand (CD40L) interaction is considered to contribute to the promotion of prothrombotic responses and production of angiogenesis-associated factor in addition to adaptive immune responses. Recently, the role of soluble CD40L (sCD40L) has gained interest in cancer, although its exact functions remain unknown. This study evaluated the clinical significance of sCD40L in patients with pancreatic ductal adenocarcinoma (PDAC) and validated its utility as a PDAC diagnostic and prognostic biomarker. METHODS: Serum sCD40L levels were measured by chemiluminescent immunoassay and compared among normal, chronic pancreatitis (CP, high-risk), and PDAC group in both training (n=25 per group) and independent validation (n=30, 30, and 55, respectively) datasets through one-way ANOVA test with the post-hoc Bonferroni method. To evaluate the diagnostic potential of serum sCD40L for PDAC, receiver operating characteristic (ROC) curves were generated and logistic regression analysis was conducted. To investigate the sCD40L-assoicated cytokines/chemokines in PDAC, cytokines/chemokines levels were analyzed by a MILLIPLEX MAP Human Cytokine/Chemokine Kit. To assess the prognostic potentials of sCD40L, Kaplan-Meier survival curve and Cox proportional-hazards regression analysis were applied. RESULTS: Serum sCD40L levels were significantly higher in PDAC group compared with non-cancer groups in both training (p<0.05) and validation (p<0.05) datasets. Clinically, serum sCD40L closely correlated with unresectability (γs=0.342, p=0.011) and distant metastasis (γs=0.294, p=0.030) of PDAC. ROC curve and logistic regression analysis demonstrated the remarkable predictive potentials of serum sCD40L for PDAC (80.0% sensitivity and 85.5% specificity at cut-off point, 0.45; logistic regression), superior to those of CA19-9 and CEA. According to cytokines/chemokines assay, serum sCD40L levels were closely correlated with serum levels of pro-angiogenic cytokines (EGF, VEGF, IL-8) and immunosuppressive cytokines (IL-6, IL-10, IL-1RA). Kaplan-Meier survival analysis demonstrated patients with high-serum sCD40L (>35,000 ng/ml) had a poorer prognosis than those with low-serum sCD40L (log-rank, p=0.015). Multivariate Cox regression analysis yielded a hazard ratio of 2.509 (95% CI, 1.038-6.067, p=0.041) for mortality in the high-serum sCD40L group. CONCLUSIONS: Serum sCD40L is correlated with immunosuppression and angiogenesis in PDAC carcinogenesis/progression, and is a promising diagnostic and prognostic biomarker for PDAC superior to CA19-9 and CEA.
Files in This Item:
T201401248.pdf Download
DOI
10.1186/1479-5876-12-102
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Lim, Jong Baeck(임종백) ORCID logo https://orcid.org/0000-0003-0419-0422
Chung, Hye Won(정혜원)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/98670
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