胰腺癌患者的血清细胞因子谱。

Serum cytokine profile in patients with pancreatic cancer.

机构信息

From the *Department of Biochemistry and Molecular Biology I, Faculty of Sciences, University of Granada; †Department of Molecular Oncology, Pfizer-University of Granada Center for Genomics and Oncological Research, Granada; ‡Department of Health Sciences, University of Jaen, Jaen; §Department of Human Anatomy and Embryology, University of Granada; ∥Oncology Service, Virgen de las Nieves Hospital; and ¶Department of Computer Architecture and Computer Technology, University of Granada, Granada, Spain.

出版信息

Pancreas. 2014 Oct;43(7):1042-9. doi: 10.1097/MPA.0000000000000155.

DOI:10.1097/MPA.0000000000000155

PMID:24979617

Abstract

OBJECTIVE

Pancreatic ductal adenocarcinoma is a deadly disease because of late diagnosis and chemoresistance. We aimed to find a panel of serum cytokines representing diagnostic and predictive biomarkers for pancreatic cancer.

METHODS

A cytokine antibody array was performed to simultaneously identify 507 cytokines in sera of patients with pancreatic cancer and healthy controls. The nonparametric Mann-Whitney U test was used to pairwise compare the controls, the pretreated patients, and the posttreated patients. Fold changes greater than or equal to 1.5 or less than or equal to 1/1.5 were considered significant. Receiver operating characteristic curves were used to assess the performance of the model. A leave-one-out cross-validation was used for estimating prediction error.

RESULTS

Comparing the sera of pretreated patients against the control samples, the cytokines fibroblast growth factor 10 (FGF-10/keratinocyte growth factor-2 (KGF-2), chemokine (C-X-C motif) ligand 11 interferon inducible T cell alpha chemokine (I-TAC)/chemokine [C-X-C motif] ligand 11 (CXCL11), oncostatin M (OSM), osteoactivin/glycoprotein nonmetastatic melanoma protein B, and stem cell factor (SCF) were found significantly overexpressed. Besides, the cytokines CD30 ligand/tumor necrosis factor superfamily, member 8 (TNFSF8), chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF were differentially expressed in response to treatment.

CONCLUSIONS

We propose a role for FGF-10/KGF-2, I-TAC/CXCL11, OSM, osteoactivin/glycoprotein nonmetastatic melanoma protein B, and SCF as novel diagnostic biomarkers. CD30 ligand/TNFSF8, chordin-like 2, FGF-10/KGF-2, growth/differentiation factor 15, I-TAC/CXCL11, OSM, and SCF might represent as predictive biomarkers for gemcitabine and erlotinib response of patients with pancreatic cancer.

摘要

目的

由于诊断较晚和化疗耐药，胰腺导管腺癌是一种致命的疾病。我们旨在寻找一组代表胰腺癌诊断和预测生物标志物的血清细胞因子。

方法

采用细胞因子抗体阵列同时鉴定胰腺癌患者和健康对照者血清中的 507 种细胞因子。采用非参数 Mann-Whitney U 检验对对照组、预处理组和后处理组进行两两比较。大于或等于 1.5 倍或小于或等于 1/1.5 倍的倍数变化被认为是显著的。使用接收者操作特征曲线评估模型的性能。采用留一法交叉验证估计预测误差。

结果

与对照样本相比，预处理患者的血清中纤维母细胞生长因子 10（FGF-10/角质细胞生长因子-2（KGF-2）、趋化因子（C-X-C 基序）配体 11 干扰素诱导 T 细胞 α趋化因子（I-TAC）/趋化因子（C-X-C 基序）配体 11（CXCL11）、肿瘤坏死因子超家族成员 11（OSM）、骨激活素/糖蛋白非转移性黑素瘤蛋白 B 和干细胞因子（SCF）表达明显升高。此外，细胞因子 CD30 配体/肿瘤坏死因子超家族成员 8（TNFSF8）、类 Chordin 2、FGF-10/KGF-2、生长/分化因子 15、I-TAC/CXCL11、OSM 和 SCF 对治疗有反应。

结论

我们提出 FGF-10/KGF-2、I-TAC/CXCL11、OSM、骨激活素/糖蛋白非转移性黑素瘤蛋白 B 和 SCF 作为新的诊断生物标志物的作用。CD30 配体/TNFSF8、类 Chordin 2、FGF-10/KGF-2、生长/分化因子 15、I-TAC/CXCL11、OSM 和 SCF 可能代表胰腺导管腺癌患者吉西他滨和厄洛替尼反应的预测生物标志物。