{Reference Type}: Journal Article
{Title}: A consensus molecular subtypes classification strategy for clinical colorectal cancer tissues.
{Author}: de Back TR;Wu T;Schafrat PJ;Ten Hoorn S;Tan M;He L;van Hooff SR;Koster J;Nijman LE;Vink GR;Beumer IJ;Elbers CC;Lenos KJ;Sommeijer DW;Wang X;Vermeulen L;
{Journal}: Life Sci Alliance
{Volume}: 7
{Issue}: 8
{Year}: 2024 Aug
{Factor}: 5.781
{DOI}: 10.26508/lsa.202402730
{Abstract}: Consensus Molecular Subtype (CMS) classification of colorectal cancer (CRC) tissues is complicated by RNA degradation upon formalin-fixed paraffin-embedded (FFPE) preservation. Here, we present an FFPE-curated CMS classifier. The CMSFFPE classifier was developed using genes with a high transcript integrity in FFPE-derived RNA. We evaluated the classification accuracy in two FFPE-RNA datasets with matched fresh-frozen (FF) RNA data, and an FF-derived RNA set. An FFPE-RNA application cohort of metastatic CRC patients was established, partly treated with anti-EGFR therapy. Key characteristics per CMS were assessed. Cross-referenced with matched benchmark FF CMS calls, the CMSFFPE classifier strongly improved classification accuracy in two FFPE datasets compared with the original CMSClassifier (63.6% versus 40.9% and 83.3% versus 66.7%, respectively). We recovered CMS-specific recurrence-free survival patterns (CMS4 versus CMS2: hazard ratio 1.75, 95% CI 1.24-2.46). Key molecular and clinical associations of the CMSs were confirmed. In particular, we demonstrated the predictive value of CMS2 and CMS3 for anti-EGFR therapy response (CMS2&3: odds ratio 5.48, 95% CI 1.10-27.27). The CMSFFPE classifier is an optimized FFPE-curated research tool for CMS classification of clinical CRC samples.