Reconciliation of classification systems defining molecular subtypes of colorectal cancer

Abstract

Recently we published two independent studies describing novel gene expression-based classifications of colorectal cancer (CRC). Notably, each study stratified CRC into a different number of subtypes: one reported 3 subtypes, whereas the second highlighted 5. Given that each ascribed clinical significance, distinctive biology, and therapeutic prognosis to the different subtypes, we sought to reconcile this apparent incongruity in subtype stratification of CRC, and to interrelate the results. To do so, we each evaluated the other's data sets and analytical methods and discovered that the subtypes and their classifiers are, in fact, clearly related to each other; indeed, the 5 subtype outcomes can be coalesced into the same three. In addition to presenting this clarification, we briefly discuss how both classification methods can be viewed within the broader literature on CRC subtypes, and potentially applied.

Extent and Location of Tumor-Infiltrating Lymphocytes in Microsatellite-Stable Colon Cancer Predict Outcome to Adjuvant Active Specific Immunotherapy

“…A close comparison between these two datasets has shown that the CCS2-MSI subgroup encompasses the inflammatory and goblet subtypes (44). According to the authors, these associations make sense also in light of previous studies (45), as MSI tumors are often associated with an inflammatory immune infiltrate and a mucinous phenotype (44).…”

GPx2 Suppression of H2O2 Stress Links the Formation of Differentiated Tumor Mass to Metastatic Capacity in Colorectal Cancer

“…GPx2 levels are associated with metastasis formation, particularly in the aggressive CCS3 subtype, which has a primitive stem-like phenotype (22,45) and is relatively resistant to current systemic therapy (22). We therefore propose that therapeutically increasing ROS levels, either through targeting GPx2 or by other means, may be particularly effective in sensitizing the aggressive colon tumor subtype to chemotherapy and/or in reducing their propensity to form metastases.…”

Caracterización de pacientes con cáncer colorrectal esporádico basado en la nueva subclasificación molecular de consenso

“…Se presenta en 15%-20% de CCR esporádicos y se le asocia a mal pronós-tico 13,14 . Debido a la heterogeneidad y complejidad de los tumores, diversos estudios han propuesto subgrupos moleculares de CCR basados en las 3 vías antes descritas [15][16][17][18][19] . Los esfuerzos en determinar el perfil molecular de CCR tienen como fin comprender mejor los mecanismos que determinan el comportamiento clínico de los diferentes tumores y, de esta manera, identificar biomarcadores que proporcionen información pronóstica precoz.…”