血清ENA78/CXCL5、SDF-1/CXCL12及其组合作为预测原发性胃癌存在和远处转移的潜在生物标志物。

Serum ENA78/CXCL5, SDF-1/CXCL12, and their combinations as potential biomarkers for prediction of the presence and distant metastasis of primary gastric cancer.

作者信息

Lim Jong-Baeck, Chung Hye Won

机构信息

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Division of Gastroenterology, International St. Mary's Hospital, Incheon Metropolitan City, Republic of Korea.

出版信息

Cytokine. 2015 May;73(1):16-22. doi: 10.1016/j.cyto.2015.01.010. Epub 2015 Feb 14.

DOI:10.1016/j.cyto.2015.01.010

PMID:25689618

Abstract

BACKGROUND

Chemokines play important roles in cancer development and progression. Epithelial-derived neutrophil-activating peptide-78 (ENA78/CXCL5) and stromal cell-derived factor (SDF-1/CXCL12) supposedly contribute to gastric cancer (GC) development and progression. This study aims to evaluate serum levels of ENA78/CXCL5 and SDF-1/CXCL12 along the GC carcinogenesis, and analyze their clinical significance, and diagnostic potentials through human serum samples.

METHODS

A total of 300 subjects were enrolled in this study. Serum levels of ENA78/CXCL5 and SDF-1/CXCL12, measured by chemiluminescent immunoassay, were compared among 4 disease groups; normal, high-risk (intestinal metaplasia and adenoma), early GC (EGC), and advanced GC (AGC) groups in both training (n=25 per group) and validation dataset (n=70, 30, 50, 50, respectively) by ANOVA test (post hoc Bonferroni). Correlations between serum ENA78/CXCL5 or SDF-1/CXCL12 levels and clinicopathological parameters of GC patients were evaluated (Spearman's correlation; γs). To validate the diagnostic accuracy, receiver operating characteristic (ROC) curve and logistic regression analysis was performed.

RESULTS

Serum ENA78/CXCL5 and SDF-1/CXCL12 levels were significantly higher in AGC groups than EGC, high-risk and normal groups in both training and validation dataset (Bonferroni, from p<0.01 to p<0.001). Clinicopathologically, serum ENA78/CXCL5 was correlated with T-stage (γs=0.231, p=0.021) and distant metastasis (γs=0.357, p<0.001), while serum SDF-1/CXCL12 was correlated with lymph node (γs=0.220, p=0.029) and distant (γs=0.425, p<0.001) metastasis. ROC curve and logistic regression demonstrated that serum ENA78/CXCL5 and SDF-1/CXCL12 showed higher diagnostic accuracy compared with carcinoembryonic antigen (CEA) in predicting GC. Serum ENA78/CXCL5 could predict both the presence of GC and distant metastasis, while serum SDF-1/CXCL12 could mainly predict its distant metastasis. All combination of serum ENA78/CXCL5, SDF-1/CXCL12, and CEA achieved 92.8% specificity at 75.0% sensitivity to predict distant metastasis of GC.

CONCLUSIONS

Combinations of initial serum ENA78/CXCL5, SDF-1/CXCL12, and CEA before any treatment for GC can produce valuable serum biomarker panels to predict the presence and distant metastasis of GC.

摘要

背景

趋化因子在癌症发展和进程中发挥重要作用。上皮来源的中性粒细胞激活肽-78（ENA78/CXCL5）和基质细胞衍生因子（SDF-1/CXCL12）可能参与胃癌（GC）的发展和进程。本研究旨在评估ENA78/CXCL5和SDF-1/CXCL12在胃癌发生过程中的血清水平，分析其临床意义，并通过人血清样本评估其诊断潜力。

方法

本研究共纳入300名受试者。通过化学发光免疫分析法测定ENA78/CXCL5和SDF-1/CXCL12的血清水平，并在训练数据集（每组n = 25）和验证数据集（分别为n = 70、30、50、50）的4个疾病组（正常、高危（肠化生和腺瘤）、早期胃癌（EGC）和进展期胃癌（AGC）组）中进行比较，采用方差分析（事后Bonferroni检验）。评估GC患者血清ENA78/CXCL5或SDF-1/CXCL12水平与临床病理参数之间的相关性（Spearman相关性；γs）。为验证诊断准确性，进行了受试者工作特征（ROC）曲线和逻辑回归分析。

结果

在训练和验证数据集中，AGC组的血清ENA78/CXCL5和SDF-1/CXCL12水平均显著高于EGC组、高危组和正常组（Bonferroni检验，p值从<0.01到<0.001）。在临床病理方面，血清ENA78/CXCL5与T分期（γs = 0.231，p = 0.021）和远处转移（γs = 0.357，p < 0.001）相关，而血清SDF-1/CXCL12与淋巴结转移（γs = 0.220，p = 0.029）和远处转移（γs = 0.425，p < 0.001）相关。ROC曲线和逻辑回归分析表明，与癌胚抗原（CEA）相比，血清ENA78/CXCL5和SDF-1/CXCL12在预测GC方面具有更高的诊断准确性。血清ENA78/CXCL5可预测GC的存在和远处转移，而血清SDF-1/CXCL12主要可预测其远处转移。血清ENA78/CXCL5、SDF-1/CXCL12和CEA的所有组合在预测GC远处转移时，在75.0%的敏感性下特异性达到92.8%。