Abstract
The high heterogeneity of colorectal cancer (CRC) is the main clinical challenge for individualized therapies. Molecular classification will contribute to drug discovery and personalized management optimizing. Here, we aimed to characterize the molecular features of CRC by a classification system based on metabolic gene expression profiles. 435 CRC samples from the Genomic Data Commons data portal were chosen as training set while 566 sample in GSE39582 were selected as testing set. Then, a non-negative matrix factorization clustering was performed, and three subclasses of CRC (C1, C2, and C3) were identified in both training set and testing set. Results showed that subclass C1 displayed high metabolic activity and good prognosis. Subclass C2 was associated with low metabolic activities and displayed high immune signatures as well as high expression of immune checkpoint genes. C2 had the worst prognosis among the three subtypes. Subclass C3 displayed intermediate metabolic activity, high gene mutation numbers and good prognosis. Finally, a 27-gene metabolism-related signature was identified for prognosis prediction. Our works deepened the understanding of metabolic hallmarks of CRC, and provided valuable information for “multi-molecular” based personalized therapies.
Highlights
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers all around the world
1,514 genes were excluded for undetectable expression or low median absolute deviation (MAD), and 1,238 genes were selected for subsequent analysis
The colorectal cancer (CRC) classification was based on metabolism-relevant genes, we further studied whether distinct subclasses in training set had different metabolic characteristics
Summary
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers all around the world. New treatment options, such as targeted therapy and immunotherapy, have been developed, the average 5-year survival probability for advanced CRC patients is still dismal, lower than 15% [3, 4]. What’s worse is that the incidence of CRC in patients who are younger than 50 years is rising sharply, and the mortality of CRC has ranked the first for men in age 20–49 during 2012 to 2016 [5, 6]. Besides the classic TNM staging based on histopathology, CRC has several molecular traits, such as chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP) [8]. With the accumulation of multiple kinds of “omics” data, CRC samples have been classified into four consensus molecular subtypes (CMS) in 2015, including CMS1 (MSI Immune, 14%), CMS2 (Canonical, 37%), CMS3 (Metabolic, 13%), and CMS4 (Mesenchymal, 23%)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
