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• W3010411332 abstract "Abstract Objective Loss of SMAD4 is associated with worse outcomes for colorectal cancer patients. We used gene ontology and bioinformatics to identify an RNA-based SMAD4-modulated profile and test its association with patient outcome. Design Using a discovery dataset of 250 colorectal cancer patients, we analyzed expression of BMP/Wnt target genes for association with SMAD4 expression. Promoters of the BMP/Wnt genes were interrogated for SMAD-binding elements. 15 genes were implicated and three tested for modulation by SMAD4 in patient-derived colorectal cancer tumoroids. Expression of the 15 genes was used for unsupervised hierarchical clustering of a training dataset and two resulting clusters modeled in a centroid model. This model was applied to an independent validation dataset of stage II and III patients. Disease-free survival was analyzed by the Kaplan-Meier method. Results In vitro analysis of three genes identified in the SMAD4-modulated profile (JAG1, TCF7, MYC) revealed modulation by SMAD4 consistent with the trend observed in the profile. In the training dataset (n = 553), the profile was not associated with outcome. However, among stage II and III patients (n = 461), distinct clusters were identified by unsupervised hierarchical clustering that were associated with disease-free survival (p = 0.02). The main model was applied to a validation dataset (n = 257) which confirmed the association of clustering with disease-free survival (p = 0.02). Conclusions A SMAD4-modulated RNA-based gene profile identified high-risk stage II and III colorectal cancer patients, can predict disease-free survival, and has prognostic potential for stage II and III colorectal cancer patients." @default.
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• W3010411332 date "2020-02-20" @default.
• W3010411332 modified "2023-10-18" @default.
• W3010411332 title "A SMAD4-modulated gene profile predicts disease-free survival in stage II and III colorectal cancer" @default.
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• W3010411332 doi "https://doi.org/10.1101/2020.02.16.20023663" @default.
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