Lin Qi, Li Jun, Zhu Dexiang, Niu Zhengchuan, Pan Xiangou, Xu Pingping, Ji Meiling, Wei Ye, Xu Jianmin
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Pharmacol. 2019 Oct 31;10:1183. doi: 10.3389/fphar.2019.01183. eCollection 2019.
Many genes and mutations have been reported for colorectal cancer (CRC); however, very few have been associated with colorectal cancer liver metastasis (CRLM). We performed gene expression profiling experiments to identify genetic markers for CRLM and elucidate the molecular mechanisms. Microarray experiments were performed on CRC primary tumor samples with or without liver metastasis (LM) using the Affymetrix U133 plus 2.0 GeneChip Array. A new identified gene-scinderin () was overexpressed with synchronous LM at both the RNA level evaluated with quantitative real-time PCR and protein level evaluated with immunohistochemistry and also with short overall survival analyzed with Kaplan-Meier method. With multivariate analysis indicated that served as an independent poor prognostic predictor for CRC patients. Disease-free survival was also significantly lower in overexpressing CRC patients with metachronous LM. In addition, knockdown significantly reduced cell proliferation, induced cell cycle arrest, and promoted the expression of some cell cycle apoptosis-related protein. Moreover, the , , , , and levels were downregulated, whereas and were upregulated in DLD-1-shSCIN cells by microarray analysis compared with DLD-1 shCon cells. These findings revealed that may serve as an important predictor of CRLM and poor outcome for CRC patients. may be a potential therapeutic target in human CRC. However, translation of its roles into clinical practice will require further investigation and additional experimental validation.
许多基因和突变已被报道与结直肠癌（CRC）相关；然而，很少有基因与结直肠癌肝转移（CRLM）相关。我们进行了基因表达谱实验，以鉴定CRLM的遗传标志物并阐明其分子机制。使用Affymetrix U133 plus 2.0基因芯片阵列对有或无肝转移（LM）的CRC原发性肿瘤样本进行了微阵列实验。一个新鉴定的基因——肌切蛋白（scinderin）在RNA水平（通过定量实时PCR评估）和蛋白质水平（通过免疫组织化学评估）均在同步肝转移时过表达，并且通过Kaplan-Meier方法分析显示其与总体生存期短相关。多变量分析表明，scinderin是CRC患者独立的不良预后预测指标。在有异时性肝转移的scinderin过表达CRC患者中，无病生存期也显著降低。此外，scinderin基因敲低显著降低细胞增殖，诱导细胞周期停滞，并促进一些细胞周期凋亡相关蛋白的表达。此外，与DLD-1 shCon细胞相比，通过微阵列分析发现，在DLD-1-shSCIN细胞中，E-cadherin、β-catenin、Vimentin、N-cadherin和MMP-9水平下调，而MMP-2和MMP-7上调。这些发现表明，scinderin可能是CRLM的重要预测指标以及CRC患者不良预后的指标。scinderin可能是人类CRC的潜在治疗靶点。然而，将其作用转化为临床实践还需要进一步研究和更多的实验验证。
