Related Experiment Video
Updated: Jan 10, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
Downregulation of Enteroendocrine Genes Predicts Survival in Colon Cancer: A Bioinformatics-Based Analysis
Eloisa Martins da Silva1, Marcella Cipelli2, Mariana Aamaral do Amaral2
1Department of Nephrology, Paulista School of Medicine, Federal University of São Paulo, Pedro de Toledo Street, 669, Vila Clementino, São Paulo 04039-032, Brazil.
Abstract:
Colorectal cancer (CRC) is the fourth most common and the third mostly deadly cancer globally. Even with alternative therapies, some patients do not respond to treatment. Identifying modulations in the tumor microenvironment (TME) of CRC is a significant challenge due to the complex and dynamic nature of the TME. The intestinal epithelium comprises different types of secretory lineage cells, including goblet, tuft, Paneth, and enteroendocrine cells (EECs). Yet the relevance of each subtype of secretory intestinal epithelial cell (IEC) within the TME is still debated. This study investigated the involvement of IECs in CRC development through an integrative bioinformatics analysis. We used publicly available datasets from the National Center for Biotechnology Information, the Cancer Genome Atlas Program, and the National Cancer Institute's Proteomics Tumor Analysis Consortium, encompassing both human and mouse CRC samples. Our findings reveal a CRC microenvironment characterized by elevated expression levels of genes associated with WNT pathway activity. Remarkably, there was increased expression of Paneth cell-associated markers and transcription factors, such as WISP1, LYZ, SOX9, and DEFA1. Conversely, EEC-specific gene markers, such as GCG (encoding glucagon-like peptide-1) and CHGA exhibited significant downregulation in CRC tissue compared with healthy tissue, partially due to Paneth cell activity. Gene ontology analysis showed species-conserved downregulation in hormone/peptide secretion-related pathways in both mouse and human CRC. Of note, lower levels of GCG and CHGA correlated with reduced overall survival and demonstrated a correlation with the cell cycle, apoptosis, and proliferation. These results suggest that the disruption of enteroendocrine cell signaling is a hallmark of CRC development and may hold prognostic and therapeutic value in treating CRC patients.
Insights
Colorectal cancer (CRC) involves changes in the tumor microenvironment, with Paneth cells increasing and enteroendocrine cells (EECs) decreasing. Disrupted EEC signaling is a key feature of CRC, impacting patient survival.
Area of Science:
- Oncology
- Bioinformatics
- Cell Biology
Background:
- Colorectal cancer (CRC) is a leading cause of cancer death globally, with treatment resistance posing a significant challenge.
- The tumor microenvironment (TME) in CRC is complex, and the specific roles of intestinal epithelial cell (IEC) subtypes are not fully understood.
- Enteroendocrine cells (EECs) are secretory cells in the intestinal epithelium, but their precise involvement in CRC development requires further investigation.
Purpose of the Study:
- To investigate the role of intestinal epithelial cells (IECs), particularly EECs and Paneth cells, in the colorectal cancer (CRC) tumor microenvironment (TME).
- To identify specific molecular alterations and signaling pathways associated with IEC subtypes in CRC development using bioinformatics approaches.
- To explore the prognostic and therapeutic potential of identified molecular changes in CRC patients.
Main Methods:
- Integrative bioinformatics analysis of publicly available datasets from NCBI, TCGA, and NCI's Proteomics Tumor Analysis Consortium.
- Analysis included both human and mouse colorectal cancer (CRC) samples.
- Gene expression analysis, Gene Ontology (GO) analysis, and correlation studies with patient survival data.
Main Results:
- The CRC microenvironment exhibits elevated WNT pathway activity and increased expression of Paneth cell markers (e.g., WISP1, LYZ, SOX9, DEFA1).
- Significant downregulation of EEC-specific gene markers, including GCG (glucagon-like peptide-1) and CHGA, was observed in CRC tissues compared to healthy tissues.
- Species-conserved downregulation of hormone/peptide secretion pathways and a correlation between lower GCG/CHGA levels and reduced overall survival, increased cell cycle activity, apoptosis, and proliferation were identified.
Conclusions:
- Disruption of enteroendocrine cell (EEC) signaling, characterized by the downregulation of key markers like GCG and CHGA, is a hallmark of colorectal cancer (CRC) development.
- The observed alterations in EECs and the interplay with Paneth cells within the tumor microenvironment (TME) suggest potential prognostic value.
- Understanding these molecular changes may offer new therapeutic strategies for treating colorectal cancer (CRC) patients.
