RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma
Colorectal cancers (CRC) are classified into consensus molecular subtypes (CMS) based on gene expression profiles. The revised classification system iCMS was proposed by considering intrinsic epithelial status, microsatellite instability (MSI), and fibrosis. This study aimed to provide molecular evi...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/19/4851 |
| _version_ | 1797576127852576768 |
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| author | Ji Won Choi Gi-Young Lee Sangsoo Kim Kwangsung Ahn In-Gu Do Kyung-Uk Jung Hyung-Ook Kim Hungdai Kim Dong-Il Park Soo-kyung Park |
| author_facet | Ji Won Choi Gi-Young Lee Sangsoo Kim Kwangsung Ahn In-Gu Do Kyung-Uk Jung Hyung-Ook Kim Hungdai Kim Dong-Il Park Soo-kyung Park |
| author_sort | Ji Won Choi |
| collection | DOAJ |
| description | Colorectal cancers (CRC) are classified into consensus molecular subtypes (CMS) based on gene expression profiles. The revised classification system iCMS was proposed by considering intrinsic epithelial status, microsatellite instability (MSI), and fibrosis. This study aimed to provide molecular evidence for the adenoma–carcinoma sequence concept by examining CRC and synchronous adenomas using iCMS. Epithelial CMS cell proportion was estimated using CiberSortx, an in silico cell fractionation method that included CMS cell types among the reference cell types. A random forest (RF) model estimated the posterior probabilities of CMS classes, which were compared with the CiberSortx results. Gene expression profiles of the published iCMS signature panel were retrieved from our dataset and subjected to heatmap clustering for classification. Bulk RNA sequencing data were collected from 29 adenocarcinomas and 11 adenoma samples. CiberSortx showed all CRC contained either CMS2 or CMS3 as the major epithelial cancer cell type. The RF model classified approximately half of the CRC as CMS4, whereas CMS4 was hardly detected by CiberSortx. Because they were enriched with myofibroblasts as per the CiberSortx classification, we tentatively designated them as iCMS2-F/iCMS3-F. iCMS coupled with the application of an in silico cell fractionation method can provide the molecular dissection of CRC and adenoma. |
| first_indexed | 2024-03-10T21:47:49Z |
| format | Article |
| id | doaj.art-9e0296e4c1904ba2ae8eccc0f947cb30 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T21:47:49Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-9e0296e4c1904ba2ae8eccc0f947cb302023-11-19T14:11:29ZengMDPI AGCancers2072-66942023-10-011519485110.3390/cancers15194851RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous AdenomaJi Won Choi0Gi-Young Lee1Sangsoo Kim2Kwangsung Ahn3In-Gu Do4Kyung-Uk Jung5Hyung-Ook Kim6Hungdai Kim7Dong-Il Park8Soo-kyung Park9Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of KoreaDepartment of Bioinformatics and Life Science, Soongsil University, Seoul 06978, Republic of KoreaDepartment of Bioinformatics and Life Science, Soongsil University, Seoul 06978, Republic of KoreaFunctional Genome Institute, PDXen Biosystems Co., Daejeon 34027, Republic of KoreaDepartment of Pathology, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of KoreaDepartment of Surgery, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of KoreaDepartment of Surgery, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of KoreaDepartment of Surgery, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of KoreaDivision of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of KoreaDivision of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, School of Medicine, Sungkyunkwan University, Seoul 03181, Republic of KoreaColorectal cancers (CRC) are classified into consensus molecular subtypes (CMS) based on gene expression profiles. The revised classification system iCMS was proposed by considering intrinsic epithelial status, microsatellite instability (MSI), and fibrosis. This study aimed to provide molecular evidence for the adenoma–carcinoma sequence concept by examining CRC and synchronous adenomas using iCMS. Epithelial CMS cell proportion was estimated using CiberSortx, an in silico cell fractionation method that included CMS cell types among the reference cell types. A random forest (RF) model estimated the posterior probabilities of CMS classes, which were compared with the CiberSortx results. Gene expression profiles of the published iCMS signature panel were retrieved from our dataset and subjected to heatmap clustering for classification. Bulk RNA sequencing data were collected from 29 adenocarcinomas and 11 adenoma samples. CiberSortx showed all CRC contained either CMS2 or CMS3 as the major epithelial cancer cell type. The RF model classified approximately half of the CRC as CMS4, whereas CMS4 was hardly detected by CiberSortx. Because they were enriched with myofibroblasts as per the CiberSortx classification, we tentatively designated them as iCMS2-F/iCMS3-F. iCMS coupled with the application of an in silico cell fractionation method can provide the molecular dissection of CRC and adenoma.https://www.mdpi.com/2072-6694/15/19/4851colorectal cancercolon polypadenomaRNA sequencing |
| spellingShingle | Ji Won Choi Gi-Young Lee Sangsoo Kim Kwangsung Ahn In-Gu Do Kyung-Uk Jung Hyung-Ook Kim Hungdai Kim Dong-Il Park Soo-kyung Park RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma Cancers colorectal cancer colon polyp adenoma RNA sequencing |
| title | RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma |
| title_full | RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma |
| title_fullStr | RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma |
| title_full_unstemmed | RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma |
| title_short | RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma |
| title_sort | rna seq based molecular classification analyses in colorectal cancer and synchronous adenoma |
| topic | colorectal cancer colon polyp adenoma RNA sequencing |
| url | https://www.mdpi.com/2072-6694/15/19/4851 |
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