Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer.
Immune-complex level of cofilin-1 in sera is associated with cancer progression and poor prognosis in pancreatic cancer.
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DOI：
10.1111/cas.13181
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发表时间：
2017-04
期刊：
影响因子：
5.7
通讯作者：
Nomura F
中科院分区：
文献类型：
--
作者：
Satoh M;Takano S;Sogawa K;Noda K;Yoshitomi H;Ishibashi M;Mogushi K;Takizawa H;Otsuka M;Shimizu H;Miyazaki M;Nomura F
胰腺导管腺癌（Pancreatic ductal adenocarcinoma，PDAC）是最致命的恶性肿瘤之一。为了改善其结果，迫切需要可靠的生物标志物。在这项研究中，我们的目的是阐明关键分子参与PDAC的进展，使用蛋白质组学方法。首先，我们进行了2-D电泳以鉴定PDAC组织中过表达的蛋白质。在琼脂糖凝胶斑点分析后，cofilin-1被鉴定并验证为通常在PDAC组织中上调的候选蛋白。在免疫组织化学中，cofilin-1在PDAC细胞的细胞质中强烈表达。根据cofilin-1的表达水平将样品分为两组。高表达组复发患者血行播散发生率明显高于低表达组（P = 0.0083）。在体外实验中，cofilin-1的敲低显著降低了PDAC细胞系中的趋化性。在我们确认cofilin-1从PDAC细胞分泌后，我们建立了血清中cofilin-1免疫复合物的检测系统。使用该系统，我们测量了血清中cofilin-1的IC水平，观察到PDAC患者中cofilin-1的IC水平高于健康志愿者和胰腺炎患者（PDAC vs.健康志愿者，P < 0.0001; PDAC vs.胰腺炎患者，P < 0.026）。值得注意的是，Cofilin-1的IC水平在PDAC进展期间显示逐步增加（P = 0.0034），并且Cofilin-1的高IC水平表明手术后患者的预后不良（P = 0.039）。这些结果表明，血清中cofilin-1的IC是PDAC预后的潜在有吸引力的血清生物标志物。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. To improve its outcome, reliable biomarkers are urgently needed. In this study, we aimed to elucidate the key molecules involved in PDAC progression using proteomics approaches. First, we undertook 2‐D electrophoresis to identify the proteins overexpressed in PDAC tissues. Following the analysis of agarose gel spots, cofilin‐1 was identified and verified as a candidate protein commonly upregulated in PDAC tissues. In immunohistochemistry, cofilin‐1 was strongly expressed in the cytoplasm of PDAC cells. Samples were divided into two groups based on the level of cofilin‐1 expression. The high expression group showed significantly higher incidence of hematogenous dissemination in relapsed patients than the low expression group (P = 0.0083). In in vitro experiments, knockdown of cofilin‐1 significantly decreased chemotaxis in PDAC cell lines. After we confirmed that cofilin‐1 was secreted from PDAC cells, we established a detection system for the immune‐complex of cofilin‐1 in sera. Using this system, we measured the IC levels of cofilin‐1 in sera and observed that the IC levels of cofilin‐1 in PDAC patients were higher than those in healthy volunteers and patients with pancreatitis (PDAC vs. healthy volunteers, P < 0.0001; PDAC vs. patients with pancreatitis, P < 0.026). Notably, the IC levels of cofilin‐1 showed a stepwise increase during PDAC progression (P = 0.0034), and high IC levels of cofilin‐1 indicated poor prognosis of patients after surgery (P = 0.039). These results suggest that the IC of cofilin‐1 in sera is a potentially attractive serum biomarker for the prognosis of PDAC.