scholarly journals A Clinically Applicable Gene-Expression Classifier Reveals Intrinsic and Extrinsic Contributions to Consensus Molecular Subtypes in Primary and Metastatic Colon Cancer

2019 ◽  
Vol 25 (14) ◽  
pp. 4431-4442 ◽  
Author(s):  
Robert Piskol ◽  
Ling Huw ◽  
Ismail Sergin ◽  
Christiaan Kljin ◽  
Zora Modrusan ◽  
...  
Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 397 ◽  
Author(s):  
Wen-Hui Wang ◽  
Ting-Yan Xie ◽  
Guang-Lei Xie ◽  
Zhong-Lu Ren ◽  
Jin-Ming Li

Identifying molecular subtypes of colorectal cancer (CRC) may allow for more rational, patient-specific treatment. Various studies have identified molecular subtypes for CRC using gene expression data, but they are inconsistent and further research is necessary. From a methodological point of view, a progressive approach is needed to identify molecular subtypes in human colon cancer using gene expression data. We propose an approach to identify the molecular subtypes of colon cancer that integrates denoising by the Bayesian robust principal component analysis (BRPCA) algorithm, hierarchical clustering by the directed bubble hierarchical tree (DBHT) algorithm, and feature gene selection by an improved differential evolution based feature selection method (DEFSW) algorithm. In this approach, the normal samples being completely and exclusively clustered into one class is considered to be the standard of reasonable clustering subtypes, and the feature selection pays attention to imbalances of samples among subtypes. With this approach, we identified the molecular subtypes of colon cancer on the mRNA gene expression dataset of 153 colon cancer samples and 19 normal control samples of the Cancer Genome Atlas (TCGA) project. The colon cancer was clustered into 7 subtypes with 44 feature genes. Our approach could identify finer subtypes of colon cancer with fewer feature genes than the other two recent studies and exhibits a generic methodology that might be applied to identify the subtypes of other cancers.


2020 ◽  
Author(s):  
R.R.J. Coebergh van den Braak ◽  
Sanne ten Hoorn ◽  
A.M. Sieuwerts ◽  
J.B. Tuynman ◽  
M. Smid ◽  
...  

Abstract Background There are profound individual differences in clinical outcome between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. Methods We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. Results CMS4 was significantly more prevalent in advanced stages of disease (III-IV). The observed differential gene expression between cancer stages is predominantly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated. CMS4 cancers showed an increased progression rate to more advanced stages. Indeed, determining CMSs was a relevant addition to TNM classification in identifying stage II colon cancer patients with high-risk of disease recurrence. Conclusions Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, also reflects distinct biological disease entities. These insights can be utilized to optimize identification of high-risk stage II colon cancers.


PLoS Medicine ◽  
2013 ◽  
Vol 10 (5) ◽  
pp. e1001453 ◽  
Author(s):  
Laetitia Marisa ◽  
Aurélien de Reyniès ◽  
Alex Duval ◽  
Janick Selves ◽  
Marie Pierre Gaub ◽  
...  

2018 ◽  
Vol 24 ◽  
pp. 309-310
Author(s):  
Mayumi Endo ◽  
Fadi Nabhan ◽  
Laura Ryan ◽  
Shumei Meng ◽  
John Phay ◽  
...  

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