XGB-BIF: An XGBoost-Driven Biomarker Identification Framework for Detecting Cancer Using Human Genomic Data

The human genome has a profound impact on human health and disease detection. Carcinoma (cancer) is one of the prominent diseases that majorly affect human health and requires the development of different treatment strategies and targeted therapies based on effective disease detection. Therefore, our research aims to identify biomarkers associated with distinct cancer types (gastric, lung, and breast) using machine learning. In the current study, we have analyzed the human genomic data of gastric cancer, breast cancer, and lung cancer patients using XGB-BIF (i.e., XGBoost-Driven Biomarker Identification Framework for detecting cancer). The proposed framework utilizes feature selection via XGBoost (eXtreme Gradient Boosting), which captures feature interactions efficiently and takes care of the non-linear effects in the genomic data. The research progressed by training XGBoost on the full dataset, ranking the features based on the Gain measure (importance), followed by the classification phase, which employed support vector machines (SVM), logistic regression (LR), and random forest (RF) models for classifying cancer-diseased and non-diseased states. To ensure interpretability and transparency, we also applied SHapley Additive exPlanations (SHAP) and Local Interpretable Model-agnostic Explanations (LIME), enabling the identification of high-impact biomarkers contributing to risk stratification. Biomarker significance is discussed primarily via pathway enrichment and by studying survival analysis (Kaplan-Meier curves, Cox regression) for identified biomarkers to strengthen translational value. Our models achieved high predictive performance, with an accuracy of more than 90%, to classify and link genomic data into diseased (cancer) and non-diseased states. Furthermore, we evaluated the models using Cohen's Kappa statistic, which confirmed strong agreement between predicted and actual risk categories, with Kappa scores ranging from 0.80 to 0.99. Our proposed framework also achieved strong predictions on the METABRIC dataset during external validation, attaining an AUC-ROC of 93%, accuracy of 0.79%, and Kappa of 74%. Through extensive experimentation, XGB-BIF identified the top biomarker genes for different cancer datasets (gastric, lung, and breast). <i>CBX2</i>, <i>CLDN1</i>, <i>SDC2</i>, <i>PGF</i>, <i>FOXS1</i>, <i>ADAMTS18</i>, <i>POLR1B</i>, and <i>PYCR3</i> were identified as important biomarkers to identify diseased and non-diseased states of gastric cancer; <i>CAVIN2</i>, <i>ADAMTS5</i>, <i>SCARA5</i>, <i>CD300LG</i>, and <i>GIPC2</i> were identified as important biomarkers for breast cancer; and <i>CLDN18</i>, <i>MYBL2</i>, <i>ASPA</i>, <i>AQP4</i>, <i>FOLR1</i>, and <i>SLC39A8</i> were identified as important biomarkers for lung cancer. XGB-BIF could be utilized for identifying biomarkers of different cancer types using genetic data, which can further help clinicians in developing targeted therapies for cancer patients.