文章：

基于RNA-Seq的结直肠癌与同步腺瘤分子分类分析

RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma

原文发布日期：4 October 2023

DOI: 10.3390/cancers15194851

类型: Article

开放获取: 是

英文摘要：

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.

摘要翻译： 

结直肠癌（CRC）根据基因表达谱被划分为共识分子亚型（CMS）。修订后的分类系统iCMS通过综合考虑上皮细胞内在状态、微卫星不稳定性（MSI）及纤维化程度而提出。本研究旨在通过应用iCMS系统检测CRC及同步腺瘤，为腺瘤-癌序列学说提供分子证据。研究采用计算细胞分选方法CiberSortx估算上皮性CMS细胞比例，该方法将CMS细胞类型纳入参考细胞类型库。通过随机森林（RF）模型估算CMS亚型的后验概率，并与CiberSortx结果进行比对。从本数据集提取已发表的iCMS特征面板基因表达谱，通过热图聚类进行分类。研究收集了29例腺癌和11例腺瘤样本的批量RNA测序数据。CiberSortx分析显示所有CRC均以CMS2或CMS3为主要上皮癌细胞类型。RF模型将约半数CRC归类为CMS4，而CiberSortx几乎未检测到CMS4亚型。根据CiberSortx分类显示这些样本富含肌成纤维细胞，我们暂将其命名为iCMS2-F/iCMS3-F。iCMS系统结合计算细胞分选方法的应用，能够为CRC及腺瘤提供分子层面的精细解析。

原文链接：

RNA-Seq-Based Molecular Classification Analyses in Colorectal Cancer and Synchronous Adenoma