Journal
CANCERS
Volume 14, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/cancers14082045
Keywords
KRAS; colorectal cancer biomarkers; gene mutations; algorithm; colorectal cancer metastasis; colorectal cancer progression
Categories
Funding
- EU Targeted therapy for advanced colorectal cancer patients (REVERT) [848 098]
- Swedish Cancer Society [CAN-2017-381]
- Swedish Children Foundation [TJ2015-0097]
- H2020-MSCA-ITN-2018-European Commission [721297]
- Swedish National Research Council [2019-01318]
- STINT Institutional Grant [IG2013-5595]
- Malmo Cancer Foundation
- Kempe STF
- Umea University
- Medical Faculty Instruments Grants
- Norland fund for Cancer Forskning
- Insamlingstiftelsen
- Bioteknik medel
- Medical Faculty infrastructure Grants, Medical Faculty, Umea University, Kempestiftelserna
- UCMR
- Bio-Film Center, Malmo University
- Swedish Research Council [2019-01318] Funding Source: Swedish Research Council
- Vinnova [2019-01318] Funding Source: Vinnova
- Forte [2019-01318] Funding Source: Forte
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We developed a new biomarker model, the 7-Gene Algorithm, using machine learning and gene mutations to predict treatment response in patients with metastatic colorectal cancer (mCRC). The algorithm showed high accuracy in predicting treatment response and has important implications for improving personalized therapies.
Simple Summary Despite the high incidence and mortality of metastatic colorectal cancer (mCRC), there are no new biomarker tools available for predicting treatment response at diagnosis. We used machine learning using gene mutations from primary tumors of patients and developed a new biomarker model termed a 7-Gene Algorithm. We showed that this algorithm can be used as a biomarker classifier to predict treatment response with better precision than the current predictive factors. The 7-Gene Algorithm showed high accuracy to predict treatment response for patients suffering mCRC. The novel 7-Gene Algorithm can be further developed as a biomarker model for improvement of personalized therapies. Purpose: Despite the high mortality of metastatic colorectal cancer (mCRC), no new biomarker tools are available for predicting treatment response. We developed gene-mutation-based algorithms as a biomarker classifier to predict treatment response with better precision than the current predictive factors. Methods: Random forest machine learning (ML) was applied to identify the candidate algorithms using the MSK Cohort (n = 471) as a training set and validated in the TCGA Cohort (n = 221). Logistic regression, progression-free survival (PFS), and univariate/multivariate Cox proportional hazard analyses were performed and the performance of the candidate algorithms was compared with the established risk parameters. Results: A novel 7-Gene Algorithm based on mutation profiles of seven KRAS-associated genes was identified. The algorithm was able to distinguish non-progressed (responder) vs. progressed (non-responder) patients with AUC of 0.97 and had predictive power for PFS with a hazard ratio (HR) of 16.9 (p < 0.001) in the MSK cohort. The predictive power of this algorithm for PFS was more pronounced in mCRC (HR = 16.9, p < 0.001, n = 388). Similarly, in the TCGA validation cohort, the algorithm had AUC of 0.98 and a significant predictive power for PFS (p < 0.001). Conclusion: The novel 7-Gene Algorithm can be further developed as a biomarker model for prediction of treatment response in mCRC patients to improve personalized therapies.
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