Gene Expression Assay: A New Panel for Early Metastatic Risk Estimation for Breast Cancer

Background: Metastasis is one of the most challenging problems in cancer diagnosis and treatment, as its causes have not been yet well characterized. Prediction of the metastatic status of breast cancer is important in cancer research because it has the potential to save lives. However, the systems biology behind metastasis is complex and driven by a variety of factors beyond those that have already been characterized for various cancer types. Furthermore, prediction of cancer metastasis is a challenging task due to the variation in parameters and conditions specific to individual patients and mutation of the sub-types. Results: In this paper, we apply tree-based machine learning algorithms for gene expression data analysis in the estimation of metastatic potentials within a group of 490 breast cancer patients. Hence, we utilize tree-based machine learning algorithms, decision trees, gradient boosting, and extremely randomized trees to assess the variable importance. Conclusions: We obtained highly accurate values from all three algorithms, we observed the highest accuracy from the Gradient Boost method which is 0.8901. Finally, we were able to determine the 10 most important genetic variables used in the boosted algorithms, as well as their respective importance scores and biological importance. Common important genes for our algorithms are found as CD8, PB1, THP-1. CD8, also known as CD8A is a receptor for the TCR, or T-cell receptor, which facilitates cytotoxic T-cell activity and its association with cancer is defined in the paper. PB1, PBRM1 or polybromo 1 is a tumor suppressor gene. THP-1 or GLI2 is a zinc finger protein referred to as ”Glioma-Associated Oncogene Family Zinc Finger 2”. This gene encodes a protein for the zinc finger, which binds DNA and mediate Sonic hedgehog signaling (SHH). Disruption in the SHH pathway have long been associated with cancer and cellular proliferation.