Discovery and validation of a 10-gene predictive signature for response to adjuvant chemotherapy in stage II and III colon cancer Journal Article
| Authors: | Xu, C.; Xia, P.; Li, J.; Lewis, K. B.; Ciombor, K. K.; Wang, L.; Smith, J. J.; Beauchamp, R. D.; Chen, X. S. |
| Article Title: | Discovery and validation of a 10-gene predictive signature for response to adjuvant chemotherapy in stage II and III colon cancer |
| Abstract: | Identifying patients with stage II and III colon cancer who will benefit from 5-fluorouracil (5-FU)-based adjuvant chemotherapy is crucial for the advancement of personalized cancer therapy. We employ a semi-supervised machine learning approach to analyze a large dataset with 933 stage II and III colon cancer samples. Our analysis leverages gene regulatory networks to discover an 18-gene prognostic signature and to explore a 10-gene signature that potentially predicts chemotherapy benefits. The 10-gene signature demonstrates strong prognostic power and shows promising potential to predict chemotherapy benefits. We establish a robust clinical assay on the NanoString nCounter platform, validated in a retrospective formalin-fixed paraffin-embedded (FFPE) cohort, which represents an important step toward clinical application. Our study lays the groundwork for improving adjuvant chemotherapy and potentially expanding into immunotherapy decision-making in colon cancer. Future prospective studies are needed to validate and establish the clinical utility of the 10-gene signature in clinical settings. © 2024 The Author(s) |
| Keywords: | controlled study; aged; middle aged; retrospective studies; genetics; fluorouracil; area under the curve; validation process; adjuvant therapy; chemotherapy, adjuvant; chemotherapy; cancer staging; outcome assessment; neoplasm staging; colorectal cancer; biomarkers; cancer immunotherapy; gene expression; gene expression profiling; colonic neoplasms; cohort analysis; drug effect; pathology; retrospective study; tumor marker; cancer therapy; prediction; gene expression regulation; gene expression regulation, neoplastic; folinic acid; colon cancer; adjuvant chemotherapy; colon tumor; gene regulatory network; drug therapy; oxaliplatin; bioinformatics; tumor gene; drug sensitivity; transcriptome; predictive value; gene regulatory networks; diagnostic test accuracy study; principal component analysis; procedures; machine learning; immune checkpoint blockade; cancer prognosis; measurement accuracy; humans; prognosis; human; male; female; article; hierarchical clustering; gene set enrichment analysis; network analysis; biomarkers, tumor; personalized cancer therapy; pathway enrichment analysis; gene network analysis; checkpoint inhibitor therapy; semi supervised machine learning |
| Journal Title: | Cell Reports Medicine |
| Volume: | 5 |
| Issue: | 8 |
| ISSN: | 2666-3791 |
| Publisher: | Cell Press |
| Date Published: | 2024-08-20 |
| Start Page: | 101661 |
| Language: | English |
| DOI: | 10.1016/j.xcrm.2024.101661 |
| PUBMED: | 39059386 |
| PROVIDER: | scopus |
| PMCID: | PMC11384724 |
| DOI/URL: | |
| Notes: | Article -- MSK corresponding author is J. Joshua Smith -- Source: Scopus |
