IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France ; INSERM, U896, Montpellier, France ; Université Montpellier1, Montpellier, France ; ICM, Institut régional du Cancer Montpellier, Montpellier, France.
PLoS One. 2013 Sep 4;8(9):e74599. doi: 10.1371/journal.pone.0074599. eCollection 2013.
To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.
为了鉴定结直肠癌肝转移中涉及的基因，我们在 13 名患者中收集了化疗前的原发肿瘤和肝转移的配对样本。我们比较了患者配对样本中的 mRNA 表达，以鉴定在转移进化过程中失调的基因。然后，我们使用不同组获得的数据验证了鉴定出的基因。在使用五种不同的微阵列平台获得的六个数据集上，该 33 基因标记能够对 87%的肝转移、98%的原发肿瘤、97%的正常结肠黏膜和 95%的正常肝组织进行分类。鉴定出的基因是特异性的结直肠癌和肝转移，因为其他转移部位和源自乳腺癌的肝转移不能被该标记分类。基因本体论术语分析表明，50%的基因与细胞外基质重塑有关，更确切地说与细胞黏附、细胞外基质组织和血管生成有关。由于该标记对结直肠癌肝转移的分类效率很高，因此鉴定出的基因代表了开发新疗法的有前途的靶点，这些新疗法将特异性地影响肝转移微环境。
