Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Ann Surg Oncol. 2012 Jul;19 Suppl 3:S518-27. doi: 10.1245/s10434-011-1993-8. Epub 2011 Aug 16.
This study was designed to identify novel and reliable serum prognostic markers in patients with colorectal cancer (CRC).
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.
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.
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.
本研究旨在鉴定结直肠癌（CRC）患者中新型且可靠的血清预后标志物。
基于细胞因子阵列分析，我们鉴定出可溶性 CXCL16 是一种新型的预后血清标志物。通过酶联免疫吸附试验（ELISA）检测 314 例 CRC 患者和 20 名正常志愿者的血清 CXCL16 水平，并研究其与包括生存在内的临床病理特征的关系。通过向 HT-29 细胞暴露于重组 CXCL16，使用增殖、侵袭和伤口愈合测定来研究可溶性 CXCL16 在 CRC 细胞中的生物学作用。
CRC 患者的中位血清 CXCL16 浓度明显高于正常志愿者。此外，血清 CXCL16 水平随着 UICC 分期分类的进展而显著升高。升高的血清 CXCL16 水平与不良生存显著相关，是 CRC 患者的独立预后标志物。此外，在接受根治性手术的 I-III 期 CRC 患者中，升高的血清 CXCL16 水平与肝同步复发和不良生存显著相关。重组可溶性 CXCL16 促进上皮-间质转化（EMT）表型，表现为 E-钙黏蛋白产生受损和波形蛋白诱导。此外，重组可溶性 CXCL16 促进 CRC 细胞系中的细胞生长、迁移和侵袭。
在本研究中，我们鉴定出 CXCL16 作为一种新型的预后标志物。术前高血清 CXCL16 水平与 CRC 患者的肝同步复发和不良预后相关。可溶性 CXCL16 可能通过诱导 EMT 在肝转移中发挥重要作用。
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