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RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma.
Ji Won Choi1,2, Gi-Young Lee3, Sangsoo Kim3
1Department of Biological Sciences, Sungkyunkwan University, Suwon 16419, Republic of Korea.
Cancers
|October 14, 2023
Summary
This study used the intrinsic Classification of Molecular Subtypes (iCMS) to analyze colorectal cancer (CRC) and adenomas. The iCMS system, combined with in silico cell fractionation, helps molecularly dissect colorectal tumors and their precursors.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Colorectal cancers (CRC) are classified using consensus molecular subtypes (CMS).
- The intrinsic Classification of Molecular Subtypes (iCMS) system refines classification by incorporating epithelial status, microsatellite instability, and fibrosis.
- Understanding the molecular progression from adenoma to carcinoma is crucial for CRC research.
Purpose of the Study:
- To provide molecular evidence supporting the adenoma-carcinoma sequence concept using the iCMS classification.
- To investigate the molecular subtypes of colorectal adenocarcinomas and synchronous adenomas.
- To evaluate the utility of in silico cell fractionation methods in conjunction with iCMS.
Main Methods:
- Utilized bulk RNA sequencing data from 29 colorectal adenocarcinomas and 11 adenoma samples.
- Employed CiberSortx, an in silico method, to estimate epithelial CMS cell proportions.
- Developed a random forest (RF) model for CMS classification and compared its results with CiberSortx.
- Applied heatmap clustering based on the iCMS signature panel.
Main Results:
- CiberSortx identified CMS2 or CMS3 as the predominant epithelial cell types in all analyzed CRCs.
- The RF model classified approximately 50% of CRCs as CMS4, a subtype poorly detected by CiberSortx.
- CRCs classified as CMS4 by RF were enriched with myofibroblasts, leading to tentative designation as iCMS2-F/iCMS3-F.
- The study demonstrated discrepancies between CiberSortx and RF model classifications for certain CRC subtypes.
Conclusions:
- The iCMS system, when integrated with in silico cell fractionation, offers a powerful approach for the molecular dissection of colorectal cancer and adenomas.
- This study provides molecular insights into the adenoma-carcinoma sequence by characterizing tumor subtypes.
- The findings highlight the importance of considering stromal components, such as myofibroblasts, in CRC molecular classification.
