Molecular Classification Based on Prognostic and Cell Cycle-Associated Genes in Patients With Colon Cancer

Abstract

The molecular classification of patients with colon cancer is inconclusive. The gene set enrichment analysis (GSEA) of dysregulated genes among normal and tumor tissues indicated that the cell cycle played a crucial role in colon cancer. We performed univariate Cox regression analysis to find out the prognostic-related genes, and these genes were then intersected with cell cycle-associated genes and were further recognized as prognostic and cell cycle-associated genes. Unsupervised non-negative matrix factorization (NMF) clustering was performed based on cell cycle-associated genes. Two subgroups were identified with different overall survival, clinical features, cell cycle enrichment profile, and mutation profile. Through nearest template prediction (NTP), the molecular classification could be effectively repeated in the original data set and validated in several independent data sets indicating that the classification is highly repeatable. Furthermore, we constructed two prognostic signatures in two subgroups, respectively. Our molecular classification based on cell cycle may provide novel insight into the treatment and the prognosis of colon cancer.

Keywords: cell cycle; colon cancer; molecular subtypes; non-negative matrix factorization; unsupervised cluster.