JPR：预测结肠癌扩散的新生物标记

    来茂德及其同事指出，在2008年，仅美国就新出现了15万例结肠癌，5万多人死于该病。然而，接受手术治疗的结肠癌患者中的一半由于癌转移到身体其他部分而在5年内复发。这组科学家说，结肠癌的转移很难探测，而且目前没有可靠的人体化学标记用于预测它的转移。
 

    为了发现用于追踪结肠癌转移的有用的生物标记，这组科学家比较了来自同一个结肠癌患者的原始肿瘤细胞与转移后的细胞产生的蛋白质。他们发现两种蛋白质在转移细胞中的浓度显著高于原始癌细胞。这组科学家说，这两种蛋白质可能作为预测结肠癌转移的血液测试的有潜力的生物标记，从而可以进行更早的干预和治疗。

    生物谷推荐原始出处：
 

    J. Proteome Res., 2010, 9 (1), pp 545–555 DOI: 10.1021/pr9008817
 

    Identification of Serum Biomarkers for Colorectal Cancer Metastasis Using a Differential Secretome Approach

    Hua Xue??, Bingjian Jun Zhang, Minliang Wu, Qiong Huang?, Qiang Wu#, Hongqiang Sheng?, Dongdong Wu?, Jianwen Hu and Maode
 

    Department of Pathology & Pathophysiology, Department of Surgical Pathology, Affiliated Women’s Hospital, Department of Clinical Pathology, Affiliated Sir Run Run Shaw Hospital, Department of Clinical Pathology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China, Department of Pathology, Anhui Medical University, Hefei, China, and Research Centre for Proteome Analysis, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
 

    Lymph node metastasis is the major concern that causes death in colorectal cancers. However, biomarkers for cancer metastasis are still lacking. In this study, we applied an LC?MS/MS-based label-free quantitative proteomics approach to compare the differential secretome of a primary cell line SW480 and its lymph node metastatic cell line SW620 from the same colorectal cancer patient. We identified a total of 910 proteins from the conditioned media and 145 differential proteins between SW480 and SW620 (>1.5-fold change). The differential expression pattern of 6 candidate proteins was validated by Western blot analysis. Among them, trefoil factor 3 and growth/differentiation factor 15, two up-regulated proteins in SW620, were further analyzed in a large cohort of clinical tissue and serum samples. Sandwich ELISA assay showed that the serum levels of both proteins were significantly higher in lymph node metastatic colorectal cancers. Receiver operating characteristic curve analysis confirmed that serum trefoil factor 3 and growth/differentiation factor 15 could provide a discriminatory diagnostic test for predicting colorectal cancer metastasis. Immunohistochemical analysis also showed that the overexpression of trefoil factor 3 or growth/differentiation factor 15 in colorectal cancer was associated with lymph node metastatic behavior. This study showed an accurate, sensitive, and robust label-free quantitation approach for differential analysis of cancer secretome. The comparison of the cancer secretome in vitro is a feasible strategy to obtain valuable biomarkers for potential clinical application. Both trefoil factor 3 and growth/differentiation factor 15 could serve as potential biomarkers for the prediction of colorectal cancer metastasis.