Cancer Metastasis Research Center, Yonsei Cancer Research Institute, Seoul, Korea.
Cancer Sci. 2010 Oct;101(10):2200-6. doi: 10.1111/j.1349-7006.2010.01666.x. Epub 2010 Aug 22.
Gastric cancer (GC) is a heterogeneous disease that is not well detected by current tumor markers. Identifying molecular markers that can predict the potential for tumor progression is important for appropriate individualized therapy. Using the Cancer Metastasis Research Center microarray database (17K cDNA microarray), we identified genes that were differentially expressed between 96 cancer and 98 normal gastric tissues using significant analysis of microarrays. From these, we selected genes that were overexpressed more than twofold in tumor tissues that encode secreted proteins. The selected genes were validated with ELISA using the sera of 96 GC patients and 48 healthy donors. Our first round of selection included 6510 genes that were differentially expressed between 96 cancer and 98 normal gastric tissues with a minimal false discovery rate of 0.005%. Out of those genes, we picked 386 that encoded secreted proteins based on the SOURCE database. Of these genes, we focused on 55 that were overexpressed more than twofold in GC compared to normal tissues. With Ingenuity Pathway Analysis, we found 34 genes related to cancer. One in particular, chemokine growth-regulated oncogene 1, CXCL1, has been linked to cancer progression in various cancer types, but not yet to GC. Levels of CXCL1 in serum samples of GC patients were significantly higher compared with healthy donors (P < 0.05). Within GC patients, CXCL1 serum levels increased according to tumor stage and lymph node metastasis. The CXCL1 gene appears to be a candidate marker for GC progression.
胃癌（GC）是一种异质性疾病，目前的肿瘤标志物不能很好地检测到。鉴定能够预测肿瘤进展潜力的分子标志物对于适当的个体化治疗非常重要。使用癌症转移研究中心微阵列数据库（17K cDNA 微阵列），我们使用微阵列分析的显著差异分析，在 96 例癌症和 98 例正常胃组织之间鉴定出差异表达的基因。从中，我们选择了在肿瘤组织中表达超过两倍的编码分泌蛋白的基因。使用 96 例 GC 患者和 48 例健康供体的血清，通过 ELISA 验证了所选基因。我们的第一轮选择包括在 96 例癌症和 98 例正常胃组织之间差异表达的 6510 个基因，假发现率最小为 0.005%。在这些基因中，我们根据 SOURCE 数据库选择了 386 个编码分泌蛋白的基因。在这些基因中，我们特别关注了与 GC 相比在正常组织中表达超过两倍的 55 个基因。通过 Ingenuity 通路分析，我们发现了 34 个与癌症相关的基因。其中一个，趋化因子生长调节癌基因 1（chemokine growth-regulated oncogene 1，CXCL1），已与多种癌症类型的癌症进展有关，但尚未与 GC 有关。GC 患者血清样本中的 CXCL1 水平明显高于健康供体（P<0.05）。在 GC 患者中，CXCL1 血清水平根据肿瘤分期和淋巴结转移而升高。CXCL1 基因似乎是 GC 进展的候选标志物。
