Modular and mechanistic changes across stages of colorectal cancer
Abstract Background While mechanisms contributing to the progression and metastasis of colorectal cancer (CRC) are well studied, cancer stage-specific mechanisms have been less comprehensively explored. This is the focus of this manuscript. Methods Using previously published data for CRC (Gene Expre...
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| Format: | Article |
| Language: | English |
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BMC
2022-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-09479-3 |
| _version_ | 1818127815588970496 |
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| author | Sara Rahiminejad Mano R. Maurya Kavitha Mukund Shankar Subramaniam |
| author_facet | Sara Rahiminejad Mano R. Maurya Kavitha Mukund Shankar Subramaniam |
| author_sort | Sara Rahiminejad |
| collection | DOAJ |
| description | Abstract Background While mechanisms contributing to the progression and metastasis of colorectal cancer (CRC) are well studied, cancer stage-specific mechanisms have been less comprehensively explored. This is the focus of this manuscript. Methods Using previously published data for CRC (Gene Expression Omnibus ID GSE21510), we identified differentially expressed genes (DEGs) across four stages of the disease. We then generated unweighted and weighted correlation networks for each of the stages. Communities within these networks were detected using the Louvain algorithm and topologically and functionally compared across stages using the normalized mutual information (NMI) metric and pathway enrichment analysis, respectively. We also used Short Time-series Expression Miner (STEM) algorithm to detect potential biomarkers having a role in CRC. Results Sixteen Thousand Sixty Two DEGs were identified between various stages (p-value ≤ 0.05). Comparing communities of different stages revealed that neighboring stages were more similar to each other than non-neighboring stages, at both topological and functional levels. A functional analysis of 24 cancer-related pathways indicated that several signaling pathways were enriched across all stages. However, the stage-unique networks were distinctly enriched only for a subset of these 24 pathways (e.g., MAPK signaling pathway in stages I-III and Notch signaling pathway in stages III and IV). We identified potential biomarkers, including HOXB8 and WNT2 with increasing, and MTUS1 and SFRP2 with decreasing trends from stages I to IV. Extracting subnetworks of 10 cancer-relevant genes and their interacting first neighbors (162 genes in total) revealed that the connectivity patterns for these genes were different across stages. For example, BRAF and CDK4, members of the Ser/Thr kinase, up-regulated in cancer, displayed changing connectivity patterns from stages I to IV. Conclusions Here, we report molecular and modular networks for various stages of CRC, providing a pseudo-temporal view of the mechanistic changes associated with the disease. Our analysis highlighted similarities at both functional and topological levels, across stages. We further identified stage-specific mechanisms and biomarkers potentially contributing to the progression of CRC. |
| first_indexed | 2024-12-11T07:23:21Z |
| format | Article |
| id | doaj.art-5cabd19471d4473389845fe6eed18466 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-11T07:23:21Z |
| publishDate | 2022-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-5cabd19471d4473389845fe6eed184662022-12-22T01:16:02ZengBMCBMC Cancer1471-24072022-04-0122111410.1186/s12885-022-09479-3Modular and mechanistic changes across stages of colorectal cancerSara Rahiminejad0Mano R. Maurya1Kavitha Mukund2Shankar Subramaniam3Department of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaDepartment of Bioengineering, University of CaliforniaAbstract Background While mechanisms contributing to the progression and metastasis of colorectal cancer (CRC) are well studied, cancer stage-specific mechanisms have been less comprehensively explored. This is the focus of this manuscript. Methods Using previously published data for CRC (Gene Expression Omnibus ID GSE21510), we identified differentially expressed genes (DEGs) across four stages of the disease. We then generated unweighted and weighted correlation networks for each of the stages. Communities within these networks were detected using the Louvain algorithm and topologically and functionally compared across stages using the normalized mutual information (NMI) metric and pathway enrichment analysis, respectively. We also used Short Time-series Expression Miner (STEM) algorithm to detect potential biomarkers having a role in CRC. Results Sixteen Thousand Sixty Two DEGs were identified between various stages (p-value ≤ 0.05). Comparing communities of different stages revealed that neighboring stages were more similar to each other than non-neighboring stages, at both topological and functional levels. A functional analysis of 24 cancer-related pathways indicated that several signaling pathways were enriched across all stages. However, the stage-unique networks were distinctly enriched only for a subset of these 24 pathways (e.g., MAPK signaling pathway in stages I-III and Notch signaling pathway in stages III and IV). We identified potential biomarkers, including HOXB8 and WNT2 with increasing, and MTUS1 and SFRP2 with decreasing trends from stages I to IV. Extracting subnetworks of 10 cancer-relevant genes and their interacting first neighbors (162 genes in total) revealed that the connectivity patterns for these genes were different across stages. For example, BRAF and CDK4, members of the Ser/Thr kinase, up-regulated in cancer, displayed changing connectivity patterns from stages I to IV. Conclusions Here, we report molecular and modular networks for various stages of CRC, providing a pseudo-temporal view of the mechanistic changes associated with the disease. Our analysis highlighted similarities at both functional and topological levels, across stages. We further identified stage-specific mechanisms and biomarkers potentially contributing to the progression of CRC.https://doi.org/10.1186/s12885-022-09479-3Colorectal cancerCRC stagesStage-specific networksStage-unique networksBiomarkersSignaling pathways |
| spellingShingle | Sara Rahiminejad Mano R. Maurya Kavitha Mukund Shankar Subramaniam Modular and mechanistic changes across stages of colorectal cancer BMC Cancer Colorectal cancer CRC stages Stage-specific networks Stage-unique networks Biomarkers Signaling pathways |
| title | Modular and mechanistic changes across stages of colorectal cancer |
| title_full | Modular and mechanistic changes across stages of colorectal cancer |
| title_fullStr | Modular and mechanistic changes across stages of colorectal cancer |
| title_full_unstemmed | Modular and mechanistic changes across stages of colorectal cancer |
| title_short | Modular and mechanistic changes across stages of colorectal cancer |
| title_sort | modular and mechanistic changes across stages of colorectal cancer |
| topic | Colorectal cancer CRC stages Stage-specific networks Stage-unique networks Biomarkers Signaling pathways |
| url | https://doi.org/10.1186/s12885-022-09479-3 |
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