Abstract
Oxaliplatin-based chemotherapy is a standard treatment for metastatic colorectal cancer (mCRC), yet accurate biomarkers to identify responders remain lacking. In this study, we developed and validated a genomic copy number alteration (CNA)-based biomarker to predict clinical response to oxaliplatin-based chemotherapy. A total of 297 samples were collected, and shallow sequencing was employed to extract CNA features. The resulting model named “CNA fingerprint” is an XGBoost model trained using 7 CNA features. The model was validated across three independent test cohorts from two centers, achieving area under the receiver operating characteristic curve (AUC) of 0.87, 0.87, and 0.85, respectively. The primary predictor was the number of DNA segments with high absolute copy numbers. Our findings suggest that the CNA fingerprint could be used as biomarker for oxaliplatin-based chemotherapy response prediction in mCRC. Further prospective clinical trials are warranted to evaluate CNA fingerprint’s performance in clinical applications.
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Acknowledgements
We thank ShanghaiTech University High Performance Computing Public Service Platform for computing services. We thank multi-omics facility, molecular and cell biology core facility of ShanghaiTech University for technical help. This work is supported by National Natural Science Foundation of China (82373149), Shanghai Science and Technology Commission (24J22800700), cross disciplinary Research Fund of Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine (JYJC202227), open project fund of the National Health Commission’s key laboratory of individualized diagnosis and treatment of nasopharyngeal cancer (2023NPCCK02) and startup funding from ShanghaiTech University.
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J.W., J.W., Z.T., and T.W. contributed equally to this work as joint first authors. X.L., X.L., and X.S.L contributed equally to this work as joint senior authors. X.S.L were responsible for overall study design. J.W., J.W., Z.T., and T.W. accessed and verified the underlying data. J.W., J.W., Z.T., T.W., K.D., J.W., N.W., Z.Y., R.Z., J.S., and X.Z. were responsible for analysis and interpretation of data. J.W., Z.T., T.W., and X.S.L. were responsible for writing, review, and/or revision of the manuscript. X.L., X.L., and X.S.L. were study supervisions and guarantors. All the authors have read, discussed, and unanimously approved the final version of the manuscript. All authors had full access to the data and had the final responsibility for the decision to submit for publication.
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Weng, J., Wang, J., Tao, Z. et al. Copy number alteration fingerprint predicts the clinical response of oxaliplatin-based chemotherapy in metastatic colorectal cancer. npj Precis. Onc. (2026). https://doi.org/10.1038/s41698-026-01354-9
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DOI: https://doi.org/10.1038/s41698-026-01354-9
