Letter Services Article: RadExpo September 2012

Jan 13, 2010
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Overview of the study design, including data collection, radiomics model construction, and biologic interpretation. (A) The primary cohort for model development and evaluation in the training and internal test sets includes 168 patients with colorectal cancer (CRC) from center 1 (Fudan University Shanghai Cancer Center), whereas external testing was performed using data from 85 patients from centers 2 (Huashan Hospital, Fudan University) and 3 (Zhongshan Hospital, Fudan University). For model interpretation, RNA sequencing (RNA-seq) data from 18 patients with CRC in center 1 and single-cell data from 35 patients from the Gene Expression Omnibus (GEO) database are incorporated. Mismatch repair (MMR) protein expression, obtained from pathologic reports in electronic medical records (EMRs), was used to identify patients with consensus molecular subtype 1 (CMS1) CRC. Tissue microarrays (TMAs) from surgically obtained CRC tissues were analyzed for immunohistochemical staining of caudal-type homeobox 2 (CDX2), 5-hydroxytryptamine receptor 2B (HTR2B), FERM domain containing 6 (FRMD6), and zinc finger E-box binding homeobox 1 (ZEB1), and the results were subsequently entered into an online classification tool that assigned patients to CMS2, 3, or 4 subtypes. (B) Radiomics workflow for CMS4 prediction. Lesions were manually delineated on T2-weighted imaging (T2WI) and contrast-enhanced (CE) T1-weighted imaging (T1WI), followed by radiomics feature extraction. Feature selection and model development were performed in the training set using machine-learning algorithms with fivefold cross-validation for model selection, and the final model was evaluated in the internal and external test sets using receiver operating characteristic (ROC) curve analysis. (C) Transcriptomic interpretation workflow. Using the radiomics-predicted CMS4 classification, bulk RNA sequencing (RNA-seq) data were used to perform differential expression analysis between predicted CMS4 and non-CMS4 groups, followed by pathway enrichment analyses to assess biologic relevance. Public single-cell RNA sequencing data from the Gene Expression Omnibus database were then used for cell-type–level interrogation to support interpretation of the associated pathways.
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Overview of the study design, including data collection, radiomics model construction, and biologic interpretation. (A) The primary cohort for model development and evaluation in the training and internal test sets includes 168 patients with colorectal cancer (CRC) from center 1 (Fudan University Shanghai Cancer Center), whereas external testing was performed using data from 85 patients from centers 2 (Huashan Hospital, Fudan University) and 3 (Zhongshan Hospital, Fudan University). For model interpretation, RNA sequencing (RNA-seq) data from 18 patients with CRC in center 1 and single-cell data from 35 patients from the Gene Expression Omnibus (GEO) database are incorporated. Mismatch repair (MMR) protein expression, obtained from pathologic reports in electronic medical records (EMRs), was used to identify patients with consensus molecular subtype 1 (CMS1) CRC. Tissue microarrays (TMAs) from surgically obtained CRC tissues were analyzed for immunohistochemical staining of caudal-type homeobox 2 (CDX2), 5-hydroxytryptamine receptor 2B (HTR2B), FERM domain containing 6 (FRMD6), and zinc finger E-box binding homeobox 1 (ZEB1), and the results were subsequently entered into an online classification tool that assigned patients to CMS2, 3, or 4 subtypes. (B) Radiomics workflow for CMS4 prediction. Lesions were manually delineated on T2-weighted imaging (T2WI) and contrast-enhanced (CE) T1-weighted imaging (T1WI), followed by radiomics feature extraction. Feature selection and model development were performed in the training set using machine-learning algorithms with fivefold cross-validation for model selection, and the final model was evaluated in the internal and external test sets using receiver operating characteristic (ROC) curve analysis. (C) Transcriptomic interpretation workflow. Using the radiomics-predicted CMS4 classification, bulk RNA sequencing (RNA-seq) data were used to perform differential expression analysis between predicted CMS4 and non-CMS4 groups, followed by pathway enrichment analyses to assess biologic relevance. Public single-cell RNA sequencing data from the Gene Expression Omnibus database were then used for cell-type–level interrogation to support interpretation of the associated pathways.
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