Multi-omics Analysis Classifies Colorectal Cancer into Distinct Methylated Immunogenic and Angiogenic Subtypes Based on Anatomical Laterality
Abstract We employed supervised machine learning algorithms to a cohort of colorectal cancer patients from the NCI to differentiate and classify the heterogenous disease based on anatomical laterality and multi-omics stratification, in a first of its kind. Multi-omics integrative analysis shows distinct clustering of left and right colorectal cancer with disentangled representation of methylome and delineation of transcriptome and genome. We present novel multi-omics findings consistent with augmented hypermethylation of genes in right CRC, epigenomic biomarkers on the right in conjunction with immune-mediated pathway signatures, and lymphocytic invasion which unlocks unique therapeutic avenues. Contrarily, left CRC multi-omics signature is found to be marked by angiogenesis, cadherins, and epithelial–mesenchymal transition (EMT). An integrated multi-omics molecular signature of RNF217-AS1, hsa-miR-10b, and panel of FBX02, FBX06, FBX044, MAD2L2, and MIIP copy number altered genes have been found by the study. Overall survival analysis reveals genomic biomarkers ABCA13 and TTN in 852 LCRC cases, and SOX11 in 170 RCRC cases that predicts a significant survival benefit. Our study exemplifies the translational competence and robustness of machine learning in effective translational bridging of research and clinic..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Indian journal of surgical oncology - 14(2023), Suppl 1 vom: 17. Mai, Seite 209-219 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
R I, Anu [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Cancer biomarkers |
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| Anmerkungen: |
© The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| doi: |
10.1007/s13193-023-01760-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
OLC2144022607 |
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| 520 | |a Abstract We employed supervised machine learning algorithms to a cohort of colorectal cancer patients from the NCI to differentiate and classify the heterogenous disease based on anatomical laterality and multi-omics stratification, in a first of its kind. Multi-omics integrative analysis shows distinct clustering of left and right colorectal cancer with disentangled representation of methylome and delineation of transcriptome and genome. We present novel multi-omics findings consistent with augmented hypermethylation of genes in right CRC, epigenomic biomarkers on the right in conjunction with immune-mediated pathway signatures, and lymphocytic invasion which unlocks unique therapeutic avenues. Contrarily, left CRC multi-omics signature is found to be marked by angiogenesis, cadherins, and epithelial–mesenchymal transition (EMT). An integrated multi-omics molecular signature of RNF217-AS1, hsa-miR-10b, and panel of FBX02, FBX06, FBX044, MAD2L2, and MIIP copy number altered genes have been found by the study. Overall survival analysis reveals genomic biomarkers ABCA13 and TTN in 852 LCRC cases, and SOX11 in 170 RCRC cases that predicts a significant survival benefit. Our study exemplifies the translational competence and robustness of machine learning in effective translational bridging of research and clinic. | ||
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Multi-omics | |
| 650 | 4 | |a Computational oncology | |
| 650 | 4 | |a Cancer biomarkers | |
| 650 | 4 | |a Molecular signature | |
| 700 | 1 | |a Vatsyayan, Aastha |4 aut | |
| 700 | 1 | |a Damodaran, Dileep |4 aut | |
| 700 | 1 | |a Sivadas, Ambily |4 aut | |
| 700 | 1 | |a Van der Speeten, Kurt |4 aut | |
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