7. Defining CRC Subtypes Based on Gene Expression Profiles
The biological and clinical diversity of CRC makes it difficult to decipher which patients benefit and respond well to adjuvant therapy [30]. Therefore, it is important to get more insight into the heterogeneity of CRC to develop individualized treatment strategies. By analyzing gene expression profiles from 1290 CRC tumors six clinically relevant CRC subtypes were recently defined as follows: goblet-like, enterocyte, stem-like, inflammatory, cetuximab-sensitive transit-amplifying (CS-TA) and cetuximab-resistent transit-amplifying (CR-TA) [31]. These subtypes are phenotypically distinct in their disease-free survival (DFS) and diversify in degree of response to chemotherapy. A development of clinically applicable assays for subtype-specific signatures and of subtype-specific therapies could lead to an effective fight against this disease. At the same time Melo and colleagues defined three subtypes of CRC using an unsupervised classification strategy of 1100 gene expression profiles. Besides chromosomal-instable and microsatellite-instable cancers they observed a third subtype, which is largely microsatellite-stable. An up-regulation of matrix remodeling and epithelial-mesenchymal transition genes accompanied by poor prognosis and low therapy response was shown for this CRC subtype [32]. Classification of tumors into these different subtypes led to the identification of applicable biomarkers that might be developed into clinical qRT-PCR or immunohistochemical assays. Thereby, CRC tumors could be classified into one of these subtypes guiding to the assignment of subtype-specific therapeutic agents.