Machine-learning derived identification of prognostic signature to forecast head and neck squamous cell carcinoma prognosis and drug response

Introduction: Head and neck squamous cell carcinoma (HNSCC), a highly heterogeneous malignancy is often associated with unfavorable prognosis. Due to its unique anatomical position and the absence of effective early inspection methods, surgical intervention alone is frequently inadequate for achieving complete remission. Therefore, the identification of reliable biomarker is crucial to enhance the accuracy of screening and treatment strategies for HNSCC.

Method: To develop and identify a machine learning-derived prognostic model (MLDPM) for HNSCC, ten machine learning algorithms, namely CoxBoost, elastic network (Enet), generalized boosted regression modeling (GBM), Lasso, Ridge, partial least squares regression for Cox (plsRcox), random survival forest (RSF), stepwise Cox, supervised principal components (SuperPC), and survival support vector machine (survival-SVM), along with 81 algorithm combinations were utilized. Time-dependent receiver operating characteristics (ROC) curves and Kaplan-Meier analysis can effectively assess the model's predictive performance. Validation was performed through a nomogram, calibration curves, univariate and multivariate Cox analysis. Further analyses included immunological profiling and gene set enrichment analyses (GSEA). Additionally, the prediction of 50% inhibitory concentration (IC50) of potential drugs between groups was determined.

Results: From analyses in the HNSCC tissues and normal tissues, we found 536 differentially expressed genes (DEGs). Subsequent univariate-cox regression analysis narrowed this list to 18 genes. A robust risk model, outperforming other clinical signatures, was then constructed using machine learning techniques. The MLDPM indicated that high-risk scores showed a greater propensity for immune escape and reduced survival rates. Dasatinib and 7 medicine showed the superior sensitivity to the high-risk NHSCC, which had potential to the clinical.

Conclusions: The construction of MLDPM effectively eliminated artificial bias by utilizing 101 algorithm combinations. This model demonstrated high accuracy in predicting HNSCC outcomes and has the potential to identify novel therapeutic targets for HNSCC patients, thus offering significant advancements in personalized treatment strategies.