Published in:
Open Access
01-12-2022 | Colorectal Cancer | Research
CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study
Authors:
Min-Er Zhong, Xin Duan, Ma-yi-di-li Ni-jia-ti, Haoning Qi, Dongwei Xu, Du Cai, Chenghang Li, Zeping Huang, Qiqi Zhu, Feng Gao, Xiaojian Wu
Published in:
Journal of Translational Medicine
|
Issue 1/2022
Login to get access
Abstract
Background
This study aimed to develop a radiogenomic prognostic prediction model for colorectal cancer (CRC) by investigating the biological and clinical relevance of intratumoural heterogeneity.
Methods
This retrospective multi-cohort study was conducted in three steps. First, we identified genomic subclones using unsupervised deconvolution analysis. Second, we established radiogenomic signatures to link radiomic features with prognostic subclone compositions in an independent radiogenomic dataset containing matched imaging and gene expression data. Finally, the prognostic value of the identified radiogenomic signatures was validated using two testing datasets containing imaging and survival information collected from separate medical centres.
Results
This multi-institutional retrospective study included 1601 patients (714 females and 887 males; mean age, 65 years ± 14 [standard deviation]) with CRC from 5 datasets. Molecular heterogeneity was identified using unsupervised deconvolution analysis of gene expression data. The relative prevalence of the two subclones associated with cell cycle and extracellular matrix pathways identified patients with significantly different survival outcomes. A radiogenomic signature-based predictive model significantly stratified patients into high- and low-risk groups with disparate disease-free survival (HR = 1.74, P = 0.003). Radiogenomic signatures were revealed as an independent predictive factor for CRC by multivariable analysis (HR = 1.59, 95% CI:1.03–2.45, P = 0.034). Functional analysis demonstrated that the 11 radiogenomic signatures were predominantly associated with extracellular matrix and immune-related pathways.
Conclusions
The identified radiogenomic signatures might be a surrogate for genomic signatures and could complement the current prognostic strategies.