Analysis of dynamic molecular networks: the progression from colorectal adenoma to cancer.
Ontology highlight
ABSTRACT: Background
Colorectal cancer (CRC) is one of the deadliest cancers worldwide. It is the fourth most deadly cancer in the world with nearly 900,000 people die every year, the progression of polyps into cancer as one of its most common developmental pathways.Methods
This study obtained gene chip data collections from the Gene Expression Omnibus for colorectal adenoma (GSE8671) and colorectal cancer (GSE32323). Differentially expressed genes (DEGs) in normal tissue and different stages of CRC were analyzed for clustering, comparison, and visualization using R software. The Cytoscape plugin DyNetViewer was used to construct a dynamic protein-protein interaction network. Subsequently, through the Database for Annotation, Visualization and Integrated Discovery, the DEGs were functionally annotated and path enriched.Results
Our study found that the matrix metalloprotein family and chemokines were the key regulatory genes that drove CRC progression. The Wnt signaling pathway, chemokine signaling pathway, and CRC pathway were the pathological pathways for CRC. Maintenance played an important role in this process. In addition, the related nodes and pathways at various stages may be potential mechanisms for promoting dynamic CRC progression.Conclusions
Our study provides a better understanding of the dynamic pattern of molecular interaction networks during CRC progression and provides relevant markers for more accurate screening of cancer in polyps.
SUBMITTER: Jiang Y
PROVIDER: S-EPMC8748073 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundColorectal carcinoma (CRC) often arises from benign adenoma after a stepwise accumulation of genetic alterations. Here, we profiled the dynamic landscapes of transcription factors (TFs) in the mucosa-adenoma-carcinoma progression sequence.MethodsThe transcriptome data of co-occurrent adenoma, carcinoma, and normal mucosa samples were obtained from GSE117606. Identification of differentially expressed TFs (DE-TFs) and subsequent function annotation were conducted in R software. Expression patterns of DE-TFs were clustered by Short Time-series Expression Miner software. Thereafter, modular co-expression analysis, Kaplan-Meier survival analysis, mutation profiling, and gene set enrichment analysis were conducted to investigate TF dynamics in colorectal tumorigenesis. Finally, tissue microarrays, including 51 tumors, 32 adenomas, and 53 normal tissues, were employed to examine the expression of significant candidates by immunohistochemistry staining.ResultsCompared to normal tissues, 20 (in adenoma samples) and 29 (in tumor samples) DE-TFs were identified. During the disease course, 28 expression patterns for DE-TFs and four co-expression modules were clustered. Notably, six DE-TFs, DACH1, GTF2IRD1, MEIS2, NR3C2, SOX9, and SPIB, were identified as having a dynamic signature along the colorectal adenoma-carcinoma sequence. The dynamic signature was of significance in GO enrichment, prognosis, and co-expression analysis. Among the 6-TF signature, the roles of GTF2IRD1, SPIB and NR3C2 in CRC progression are unclear. Immunohistochemistry validation showed that GTF2IRD1 enhanced significantly throughout the mucosa-adenoma-carcinoma sequence, while SPIB and NR3C2 kept decreasing in stroma during the disease course.ConclusionsOur study provided a dynamic 6-TF signature throughout the course of colorectal mucosa-adenoma-carcinoma. These findings deepened the understanding of colorectal cancer pathogenesis.
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