The aim of this pilot study was to identify proteins associated with advancement of colon cancer (CC). A quantitative proteomics approach was used to determine the global changes in the proteome of primary colon cancer from patients with non-cancer normal colon (NC), non-adenomatous colon polyp (NAP), non-metastatic tumor (CC NM) and metastatic tumor (CC M) tissues, to identify up- and down-regulated proteins. Total protein was extracted from each biopsy, trypsin-digested, iTRAQ-labeled and the resulting peptides separated using strong cation exchange (SCX) and reverse-phase (RP) chromatography on-line to electrospray ionization mass spectrometry (ESI-MS). Database searching of the MS/MS data resulted in the identification of 2777 proteins which were clustered into groups associated with disease progression. Proteins which were changed in all disease stages including benign, and hence indicative of the earliest molecular perturbations, were strongly associated with spliceosomal activity, cell cycle division, and stromal and cytoskeleton disruption reflecting increased proliferation and expansion into the surrounding healthy tissue. Those proteins changed in cancer stages but not in benign, were linked to inflammation/immune response, loss of cell adhesion, mitochondrial function and autophagy, demonstrating early evidence of cells within the nutrient-poor solid mass either undergoing cell death or adjusting for survival. Caveolin-1, which decreased and Matrix metalloproteinase-9, which increased through the three disease stages compared to normal tissue, was selected to validate the proteomics results, but significant patient-to-patient variation obfuscated interpretation so corroborated the contradictory observations made by others. Nevertheless, the study has provided significant insights into CC stage progression for further investigation.

中文翻译：

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结肠癌进展的蛋白质组学分析

这项初步研究的目的是鉴定与结肠癌 (CC) 进展相关的蛋白质。定量蛋白质组学方法用于确定非癌正常结肠 (NC)、非腺瘤性结肠息肉 (NAP)、非转移性肿瘤 (CC NM) 和转移性肿瘤患者的原发性结肠癌蛋白质组的整体变化(CC M) 组织，以识别上调和下调的蛋白质。从每个活组织检查中提取总蛋白质，胰蛋白酶消化，iTRAQ 标记，并使用强阳离子交换 (SCX) 和反相 (RP) 色谱在线分离电喷雾电离质谱 (ESI-MS)。对 MS/MS 数据的数据库搜索导致识别出 2777 种蛋白质，这些蛋白质被归类为与疾病进展相关的组。在包括良性在内的所有疾病阶段发生变化的蛋白质，因此表明最早的分子扰动，与剪接体活性、细胞周期分裂以及基质和细胞骨架破坏密切相关，反映了增殖和扩展到周围健康组织的增加。这些蛋白质在癌症阶段发生了变化，但在良性阶段没有变化，与炎症/免疫反应、细胞粘附丧失、线粒体功能和自噬有关，这表明早期证据表明，营养贫乏的固体物质中的细胞正在经历细胞死亡或为生存而调整。选择与正常组织相比减少的 Caveolin-1 和在三个疾病阶段增加的 Matrix metalloproteinase-9 来验证蛋白质组学结果，但显着的患者间差异混淆了解释，因此证实了其他人的矛盾观察。然而，该研究为进一步研究 CC 阶段进展提供了重要的见解。