Soluble CXCL16 in Preoperative Serum is a Novel Prognostic Marker and Predicts Recurrence of Liver Metastases in Colorectal Cancer Patients
Soluble CXCL16 in Preoperative Serum is a Novel Prognostic Marker and Predicts Recurrence of Liver Metastases in Colorectal Cancer Patients
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DOI：
10.1245/s10434-011-1993-8
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发表时间：
2012-07-01
影响因子：
3.7
通讯作者：
Kusunoki, Masato
中科院分区：
文献类型：
--
作者：
Matsushita, Kohei;Toiyama, Yuji;Kusunoki, Masato
目的。本研究旨在确定结直肠癌（CRC）患者新的可靠的血清预后标志物。方法。基于细胞因子阵列分析，我们发现可溶性CXCL16是一种新的预后血清标志物。采用酶联免疫吸附法检测314例结直肠癌患者和20例正常志愿者血清CXCL16水平，并研究其与临床病理表现（包括生存率）的关系。通过将重组CXCL16暴露于HT-29细胞中，采用增殖、侵袭和伤口愈合实验来研究可溶性CXCL16在结直肠癌细胞中的生物学作用。结果。结直肠癌患者血清中位CXCL16浓度显著高于正常志愿者。此外，血清CXCL16水平随UICC分期的进展而显著升高。血清CXCL16水平升高与生存不良显著相关，是结直肠癌患者的独立预后指标。此外，在接受治疗目的手术的I-III期CRC患者中，血清CXCL16水平升高与异时性肝脏复发和生存不良显著相关。在体外，重组可溶性CXCL16促进上皮-间质转化（EMT）表型，其特征是E-cadherin的产生受损和vimentin的诱导。此外，重组可溶性CXCL16促进结直肠癌细胞系的细胞生长、迁移和侵袭。结论。在这项研究中，我们发现CXCL16是一种新的预后标志物。术前高水平的CXCL16与CRC患者肝脏异时性复发及预后不良相关。可溶性CXCL16可能通过诱导EMT在肝转移中发挥重要作用。
Purpose. This study was designed to identify novel and reliable serum prognostic markers in patients with colorectal cancer (CRC). Methods. Based on cytokine array analysis, we identified soluble CXCL16 as a novel prognostic serum marker. Serum levels of CXCL16 were assessed in 314 CRC patients and 20 normal volunteers by enzyme-linked immunosorbent assay, and their relationships with clinicopathologic findings, including survival, were investigated. Proliferation, invasion, and wound healing assays were used to investigate the biological role of soluble CXCL16 in CRC cells, by exposure of HT-29 cells to recombinant CXCL16. Results. The median serum CXCL16 concentration in CRC patients was significantly higher than that in normal volunteers. In addition, serum CXCL16 levels increased significantly in accordance with the progression of UICC stage classification. Elevated serum CXCL16 level was significantly associated with poor survival and was an independent prognostic marker in CRC patients. Furthermore, in stage I-III CRC patients who underwent curative intent surgery, elevated serum CXCL16 levels were significantly associated with metachronous liver recurrence and poor survival. Recombinant soluble CXCL16 promoted the epithelial-mesenchymal transition (EMT) phenotype characterized by impaired E-cadherin production and induction of vimentin in vitro. In addition, recombinant soluble CXCL16 promoted cell growth, migration, and invasion in a CRC cell line. Conclusions. In this study, we identified CXCL16 as a novel prognostic marker. Preoperative high serum levels of CXCL16 were associated with metachronous liver recurrence and poor prognosis in CRC patients. Soluble CXCL16 may play an important role in liver metastases through the induction of EMT.