Cherradi Sara, Martineau Pierre, Gongora Céline, Del Rio Maguy
Institut de Recherche en Cancérologie de Montpellier (IRCM), INSERM U1194, Université de Montpellier, Institut régional du Cancer de Montpellier, Montpellier F-34298, France,
Cancer Manag Res. 2019 Feb 13;11:1337-1348. doi: 10.2147/CMAR.S188192. eCollection 2019.
Colorectal cancer (CRC) is a heterogeneous disease that can be classified into distinct molecular subtypes. The aims of this study were 1) to compare claudin () gene expression in CRC samples and normal colon mucosa, and then in the different CRC molecular subtypes, and 2) to assess their prognostic value.
expression in CRC samples was analyzed using gene expression data for a cohort of 143 primary CRC samples, and compared in the same CRC samples classified into different molecular subtypes (C1 to C6 according to the Marisa's classification, and CMS1 to CMS4 of the consensus classification). Comparison of expression in normal and tumor colon samples was also made on a smaller number of samples. Then, the relationship between expression profiles and overall survival (OS) and progression-free survival was examined.
Compared with normal mucosa, and were upregulated, whereas , , , and were downregulated in CRC samples. Variations in expression profiles were observed mainly in the CMS2/C1 and CMS4/C4 subtypes. Overall, expression of or alone had a strong prognostic value that increased when they were associated. In the CMS4/C4 subtypes, lower expressions of , , and were associated with longer OS. Conversely, in the CMS2 and C1 subtypes, low expression was associated with shorter OS and progression-free survival, suggesting a dual role for as a tumor suppressor/promoter in CRC. and had a prognostic value in the CMS2 and C4 subtypes, respectively.
This analysis of gene expression profiles and prognostic value in CRC samples classified according to their molecular subtype shows that CRC heterogeneity must be taken into account when assessing potential value as prognostic markers or therapeutic targets.
结直肠癌（CRC）是一种异质性疾病，可分为不同的分子亚型。本研究的目的是：1）比较claudin（）基因在CRC样本和正常结肠黏膜中的表达，然后在不同的CRC分子亚型中进行比较；2）评估它们的预后价值。
使用143例原发性CRC样本队列的基因表达数据，分析CRC样本中的表达，并在分为不同分子亚型（根据玛丽莎分类法为C1至C6，以及共识分类法中的CMS1至CMS4）的相同CRC样本中进行比较。还对少量样本进行了正常和肿瘤结肠样本中表达的比较。然后，研究了表达谱与总生存期（OS）和无进展生存期之间的关系。
与正常黏膜相比，CRC样本中 和 上调，而 、 、 和 下调。主要在CMS2/C1和CMS4/C4亚型中观察到表达谱的变化。总体而言，单独的 或 的表达具有很强的预后价值，当它们联合时预后价值增加。在CMS4/C4亚型中， 、 和 的低表达与较长的OS相关。相反，在CMS2和C1亚型中，低表达与较短的OS和无进展生存期相关，表明 在CRC中作为肿瘤抑制因子/促进因子具有双重作用。 和 分别在CMS2和C4亚型中具有预后价值。
对根据分子亚型分类的CRC样本中的 基因表达谱和预后价值进行的分析表明，在评估 作为预后标志物或治疗靶点的潜在价值时，必须考虑CRC的异质性。
