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Title: | Multi-omics Analysis Classifies Colorectal Cancer into Distinct Methylated Immunogenic and Angiogenic Subtypes Based on Anatomical Laterality | Authors: | Anu, R., I Vatsyayan, Aastha Damodaran, Dileep Sivadas, Ambily VAN DER SPEETEN, Kurt |
Issue Date: | 2023 | Publisher: | SPRINGER INDIA | Source: | INDIAN JOURNAL OF SURGICAL ONCOLOGY, 14 , p. 209-219 | Abstract: | Weemployed 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. | Notes: | Anu, RI (corresponding author), MVR Canc Ctr & Res Inst, Dept Canc Biol & Therapeut, Calicut, Kerala, India.; Anu, RI (corresponding author), MVR Canc Ctr & Res Inst, Dept Clin Biochem, Calicut, Kerala, India. dranu@alumni.harvard.edu |
Keywords: | Colorectal cancer;Multi-omics;Computational oncology;Cancer biomarkers;Molecular signature | Document URI: | http://hdl.handle.net/1942/40274 | ISSN: | 0975-7651 | e-ISSN: | 0976-6952 | DOI: | 10.1007/s13193-023-01760-6 | ISI #: | 000989809500001 | Rights: | The Author(s), under exclusive licence to Indian Association of Surgical Oncology 2023 | Category: | A1 | Type: | Journal Contribution |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
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IJSO Revised Manuscript.pdf Until 2024-06-30 | Peer-reviewed author version | 1.22 MB | Adobe PDF | View/Open Request a copy |
s13193-023-01760-6 (1).pdf Restricted Access | Published version | 2.66 MB | Adobe PDF | View/Open Request a copy |
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