CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study
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 identifi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-022-03788-8 |
| _version_ | 1828091206537576448 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Min-Er Zhong |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T06:09:26Z |
| format | Article |
| id | doaj.art-2f933b3cd3f649239a4ef4b62a4686a4 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T06:09:26Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-2f933b3cd3f649239a4ef4b62a4686a42022-12-22T04:41:20ZengBMCJournal of Translational Medicine1479-58762022-12-0120111210.1186/s12967-022-03788-8CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective studyMin-Er Zhong0Xin Duan1Ma-yi-di-li Ni-jia-ti2Haoning Qi3Dongwei Xu4Du Cai5Chenghang Li6Zeping Huang7Qiqi Zhu8Feng Gao9Xiaojian Wu10Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversitySchool of Biomedical Engineering, Shenzhen Campus of Sun Yat-sen UniversityDepartment of Radiology, The First People’s Hospital of Kashi PrefectureDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityDepartment of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen UniversityAbstract 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.https://doi.org/10.1186/s12967-022-03788-8Colorectal cancerRadiogenomicIntratumor heterogeneityPrognosisSignature |
| spellingShingle | 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 CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study Journal of Translational Medicine Colorectal cancer Radiogenomic Intratumor heterogeneity Prognosis Signature |
| title | CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study |
| title_full | CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study |
| title_fullStr | CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study |
| title_full_unstemmed | CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study |
| title_short | CT-based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer: a multi-institutional retrospective study |
| title_sort | ct based radiogenomic analysis dissects intratumor heterogeneity and predicts prognosis of colorectal cancer a multi institutional retrospective study |
| topic | Colorectal cancer Radiogenomic Intratumor heterogeneity Prognosis Signature |
| url | https://doi.org/10.1186/s12967-022-03788-8 |
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