Claudin gene expression profiles and clinical value in colorectal tumors classified according to their molecular subtype.

PURPOSE

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.

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.