Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis
Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity—a worldwide public health concern—is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106217/?tool=EBI |
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| author | Michael W. Greene Peter T. Abraham Peyton C. Kuhlers Elizabeth A. Lipke Martin J. Heslin Stanley T. Wijaya Ifeoluwa Odeniyi |
| author_facet | Michael W. Greene Peter T. Abraham Peyton C. Kuhlers Elizabeth A. Lipke Martin J. Heslin Stanley T. Wijaya Ifeoluwa Odeniyi |
| author_sort | Michael W. Greene |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity—a worldwide public health concern—is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas–Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; body mass index (BMI) was calculated and categorized as normal, overweight, and obese. We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing associations on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Our findings support that obesity impacts the CRC tumor transcriptome in a CMS-specific manner. The possible associations reported here are preliminary and will require validation using in vitro and animal models to examine the CMS-dependence of the genes and pathways. Once validated the obesity-linked genes and pathways may represent new therapeutic targets to treat colon cancer in a CMS-dependent manner. |
| first_indexed | 2024-04-14T05:39:19Z |
| format | Article |
| id | doaj.art-720c327d86d548c6946a89286c2e7887 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T05:39:19Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-720c327d86d548c6946a89286c2e78872022-12-22T02:09:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01175Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysisMichael W. GreenePeter T. AbrahamPeyton C. KuhlersElizabeth A. LipkeMartin J. HeslinStanley T. WijayaIfeoluwa OdeniyiColorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity—a worldwide public health concern—is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas–Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; body mass index (BMI) was calculated and categorized as normal, overweight, and obese. We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing associations on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Our findings support that obesity impacts the CRC tumor transcriptome in a CMS-specific manner. The possible associations reported here are preliminary and will require validation using in vitro and animal models to examine the CMS-dependence of the genes and pathways. Once validated the obesity-linked genes and pathways may represent new therapeutic targets to treat colon cancer in a CMS-dependent manner.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106217/?tool=EBI |
| spellingShingle | Michael W. Greene Peter T. Abraham Peyton C. Kuhlers Elizabeth A. Lipke Martin J. Heslin Stanley T. Wijaya Ifeoluwa Odeniyi Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis PLoS ONE |
| title | Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis |
| title_full | Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis |
| title_fullStr | Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis |
| title_full_unstemmed | Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis |
| title_short | Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis |
| title_sort | consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106217/?tool=EBI |
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