Successful identification of a predictive biomarker for lymph node metastasis in colorectal cancer using a proteomic approach.
Successful identification of a predictive biomarker for lymph node metastasis in colorectal cancer using a proteomic approach.
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DOI：
10.18632/oncotarget.22149
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发表时间：
2017-12-05
期刊：
影响因子：
--
通讯作者：
Kusunoki M
中科院分区：
文献类型：
--
作者：
Mori K;Toiyama Y;Otake K;Ide S;Imaoka H;Okigami M;Okugawa Y;Fujikawa H;Saigusa S;Hiro J;Kobayashi M;Ohi M;Tanaka K;Inoue Y;Kobayashi Y;Mohri Y;Kobayashi I;Goel A;Kusunoki M
结直肠癌 (CRC) 相关死亡率主要由淋巴结 (LN) 和远处转移引起，这凸显了对预测 LN 转移并促进更好的治疗策略的生物标志物的需求。我们使用基于相对和绝对定量同量异位标签 (iTRAQ) 的比较蛋白质组学方法来鉴定用于预测 CRC 患者 LN 转移的新型生物标志物。我们分析了五对有或无淋巴结转移、邻近正常粘膜和正常结肠粘膜的 CRC 样本，并鉴定了差异表达的蛋白质，随后分别通过免疫组织化学和 qRT-PCR 在蛋白质和/或 mRNA 水平上进行了验证。我们鉴定了 55 种与 LN 转移特异性相关的蛋白质，从中选择埃兹蛋白进行进一步分析和功能评估。 CRC组织中ezrin蛋白和mRNA水平的表达均显着高于邻近正常结肠粘膜。在单变量分析中，ezrin高表达与肿瘤进展和不良预后显着相关，这与我们的体外研究结果一致，即ezrin通过使细胞侵袭和迁移来促进CRC细胞的转移能力。在多变量分析中，CRC 样本中高水平的埃兹蛋白和 mRNA 是 LN 转移的独立预测因子。因此，我们的数据将 ezrin 确定为预测 CRC 患者 LN 转移的新型蛋白质和 mRNA 生物标志物。
Colorectal cancer (CRC)-associated mortality is primarily caused by lymph node (LN) and distant metastasis, highlighting the need for biomarkers that predict LN metastasis and facilitate better therapeutic strategies. We used an Isobaric Tags for Relative and Absolute Quantification (iTRAQ)-based comparative proteomics approach to identify novel biomarkers for predicting LN metastasis in CRC patients. We analyzed five paired samples of CRC with or without LN metastasis, adjacent normal mucosa, and normal colon mucosa, and differentially expressed proteins were identified and subsequently validated at the protein and/or mRNA levels by immunohistochemistry and qRT-PCR, respectively. We identified 55 proteins specifically associated with LN metastasis, from which we selected ezrin for further analysis and functional assessment. Expression of ezrin at both the protein and mRNA levels was significantly higher in CRC tissues than in adjacent normal colonic mucosa. In univariate analysis, high ezrin expression was significantly associated with tumor progression and poor prognosis, which was consistent with our in vitro findings that ezrin promotes the metastatic capacity of CRC cells by enabling cell invasion and migration. In multivariate analysis, high levels of ezrin protein and mRNA in CRC samples were independent predictors of LN metastasis. Our data thus identify ezrin as a novel protein and mRNA biomarker for predicting LN metastasis in CRC patients.
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