Hierarchical clustering identifies a subgroup of colonic adenocarcinomas expressing crypt-like differentiation markers, associated with MSS status and better prognosis

Abstract

The aim of this study was to identify in the group of colonic adenocarcinomas, not otherwise specified (NOS), subgroups of oncogenetic and prognostic significance based on the expression of immunohistochemical markers of epithelial cell differentiation of the gastrointestinal tract. Hierarchical clustering analysis of 122 adenocarcinomas (NOS) identified four clusters based on how closely their profile of immunohistochemical expression of differentiation markers was related: (i) a major cluster of 83 adenocarcinomas (68%) called crypt-like carcinoma (CLA) with a immunohistochemically expressing colonic crypt differentiation markers (cytokeratin 20+, CDX2+, MUC2+ or MUC2-) and (ii) three minor clusters, characterized by the loss of colonic crypt differentiation markers and/or the acquisition of expression of markers of metaplastic foveolar gastric differentiation (MUC5AC+) and/or aberrant cytokeratin 7 expression. CLAs were invariably MSS (χ (2) test: p < 0.0001). The sole parameters associated with worse overall survival of the 122 patients with adenocarcinoma (NOS) were pT stage, pN+ stage, and advanced clinical stage. Interestingly, CLA lineage of differentiation was an independent prognostic parameter for better overall survival among the 40 patients with an adenocarcinoma (NOS) stage III. In conclusion, hierarchical clustering led to the identification of a main cluster of adenocarcinoma (NOS) with crypt-like differentiation, associated with MSS status and better prognosis. Its value as a biomarker of response to conventional chemotherapeutic agents deserves to be examined in randomized therapy trials.

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

“…Our analysis of the prognostic role of CK7 was performed retrospectively and without knowledge of BRAF status. Droy-Dupré et al clustered 122 CRCs describing CK20 + CK7-CDX2 + MMR + so called "crypt-like carcinoma" and minor MUC5AC + CK7+/-subtype with foveolar gastric phenotype; the latter cluster of CRCs displayed worse prognosis [20]. However, this study is not directly comparable to ours because of different way of cohort grouping based on different examined markers.…”

“…It is taken as a good distinguishing marker for primary lung cancer and CRC metastatic spread to the lungs, but not all CRCs lack CK7 expression. Various studies have shown that the rate of CK7-positivity can vary from 0 to 22% [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20].…”

Delineation of molecular pathway activities of the chronic antidepressant treatment response suggests important roles for glutamatergic and ubiquitin–proteasome systems

“…It has been applied to identify subgroups of cells and animals based on marker protein expression or behavioural parameters. 19, 20 Hierarchical clustering analysis was carried out with SPSS (SPSS version 21, IBM SPSS, Chicago, IL, USA) to separate vehicle- or paroxetine-treated mice into subgroups. Based on FST immobility time, three subgroups that include long-time floating, intermediate-time floating and short-time floating groups were stratified for each treatment condition (vehicle or paroxetine).…”

Purine and pyrimidine metabolism: Convergent evidence on chronic antidepressant treatment response in mice and humans

“…HCA is a method to build and split different cluster hierarchies. It has been applied to identify sub-groups of cells and animals based on marker protein expression or behavioral parameters 40 41 . HCA was carried out with SPSS (SPSS version 21, IBM SPSS Inc., Chicago, IL, USA) to separate paroxetine-treated sub-groups of mice based on FST floating time.…”