ArticleCancer reports (Hoboken, N.J.)2022
A SMAD4-modulated gene profile predicts disease-free survival in stage II and III colorectal cancer.
Article in Cancer reports (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 29 citations in OpenAlex.
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- Integrative analysis of multi-omics data and gut microbiota composition reveals prognostic subtypes and predicts immunotherapy response in colorectal cancer using machine learning.Scientific reports · 2025Article
- Prognostic role of tumor microenvironment and immune- and autophagy-related genes in colorectal adenocarcinoma.Translational cancer research · 2025Article
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- PRMT5 highly expressed on CD16 + CD56- natural killer cells is correlated with NK cells exhaustion in colorectal cancer mesenchyme.Cancer immunology, immunotherapy : CII · 2025Article
- Downregulation of SMAD2 and SMAD4 is associated with poor prognosis and shorter survival in esophageal squamous cell carcinoma.Molecular biology reports · 2025Article
- A machine learning-based prognostic model integrating mRNA stemness index, hypoxia, and glycolysis‑related biomarkers for colorectal cancer.Open medicine (Warsaw, Poland) · 2025Article
- Glycolysis-Driven Immune Evasion in Microsatellite Instability-High Colorectal Cancer: An Integrated Single-Cell and Spatial Transcriptomics Study.OncoTargets and therapy · 2025Article
- Single-cell and spatial transcriptomic analysis reveals tumor cell heterogeneity and underlying molecular program in colorectal cancer.Frontiers in immunology · 2025Article
- Genetic and microenvironmental evolution of colorectal liver metastases under chemotherapy.Cell reports. Medicine · 2024Article
- Integrative multi-omics profiling of colorectal cancer from a Hispanic/Latino cohort of patients.medRxiv : the preprint server for health sciences · 2024Article
- Organ preservation after neoadjuvant long-course chemoradiotherapy versus short-course radiotherapy.Annals of oncology : official journal of the European Society for Medical Oncology · 2024Article
- Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.Journal of translational medicine · 2024Article
- M2 Macrophage Classification of Colorectal Cancer Reveals Intrinsic Connections with Metabolism Reprogramming and Clinical Characteristics.Pharmacogenomics and personalized medicine · 2024Article
- LWJ-M30, a conjugate of DM1 and B6, for the targeted therapy of colorectal cancer with improved therapeutic effects.RSC advances · 2023Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundColorectal cancer is the second-leading cause of cancer-related mortality in the United States and a leading cause of cancer-related mortality worldwide. Loss of SMAD4, a critical tumor suppressor and the central node of the transforming growth factor-beta superfamily, is associated with worse outcomes for colorectal cancer patients; however, it is unknown whether an RNA-based profile associated with SMAD4 expression could be used to better identify high-risk colorectal cancer patients.
aimIdentify a gene expression-based SMAD4-modulated profile and test its association with patient outcome. METHODS AND
resultsUsing 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. Fifteen 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. In vitro analysis of three genes identified in the SMAD4-modulated profile (JAG1, TCF7, and 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 = .02, log-rank test). The main model was applied to a validation dataset of stage II/III CRC patients (n = 257) which confirmed the association of clustering with disease-free survival (p = .013, log-rank test).
conclusionsA SMAD4-modulated gene expression 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.
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