This paper documents the process by which we, through gene and
miRNA expression profiling of the same samples of
head and neck squamous cell carcinomas (
HNSCC) and an integrative
miRNA-
mRNA expression analysis, were able to identify candidate
biomarkers of progression-free survival (PFS) in patients treated with
cetuximab-based approaches. Through sparse partial least square-discriminant analysis (sPLS-DA) and supervised analysis, 36
miRNAs were identified in two components that clearly separated long- and short-PFS patients. Gene set enrichment analysis identified a significant correlation between the
miRNA first-component and EGFR signaling, keratinocyte differentiation, and p53. Another significant correlation was identified between the second component and RAS, NOTCH, immune/inflammatory response, epithelial-mesenchymal transition (EMT), and angiogenesis pathways. Regularized canonical correlation analysis of sPLS-DA
miRNA and gene data combined with the MAGIA2 web-tool highlighted 16
miRNAs and 84 genes that were interconnected in a total of 245 interactions. After feature selection by a smoothed t-statistic support vector machine, we identified three
miRNAs and five genes in the
miRNA-gene network whose expression result was the most relevant in predicting PFS (Area Under the Curve, AUC = 0.992). Overall, using a well-defined clinical setting and up-to-date bioinformatics tools, we are able to give the proof of principle that an integrative
miRNA-
mRNA expression could greatly contribute to the refinement of the biology behind a predictive model.