title: Toward Signaling-Driven Biomarkers Immune to Normal Tissue Contamination.
abstract: The goal of this study was to discover a minimally invasive pathway-specific biomarker that is immune to normal cell mRNA contamination for diagnosing head and neck squamous cell carcinoma (HNSCC). Using Elsevier's MedScan natural language processing component of the Pathway Studio software and the TRANSFAC database, we produced a curated set of genes regulated by the signaling networks driving the development of HNSCC. The network and its gene targets provided prior probabilities for gene expression, which guided our CoGAPS matrix factorization algorithm to isolate patterns related to HNSCC signaling activity from a microarray-based study. Using patterns that distinguished normal from tumor samples, we identified a reduced set of genes to analyze with Top Scoring Pair in order to produce a potential biomarker for HNSCC. Our proposed biomarker comprises targets of the transcription factor (TF) HIF1A and the FOXO family of TFs coupled with genes that show remarkable stability across all normal tissues. Based on validation with novel data from The Cancer Genome Atlas (TCGA), measured by RNAseq, and bootstrap sampling, the biomarker for normal vs. tumor has an accuracy of 0.77, a Matthews correlation coefficient of 0.54, and an area under the curve (AUC) of 0.82.
authors.affiliation: Department of Mathematics and Statistics, The College of New Jersey, Ewing, NJ, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Stansfield
authors.affiliation: Department of Mathematics and Statistics, The College of New Jersey, Ewing, NJ, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rusay
authors.affiliation: Department of Mathematics and Statistics, The College of New Jersey, Ewing, NJ, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Shan
authors.affiliation: Department of Mathematics and Statistics, The College of New Jersey, Ewing, NJ, USA.
authors.forename: Conor
authors.initials: C
authors.lastname: Kelton
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Daria A
authors.initials: DA
authors.lastname: Gaykalova
authors.affiliation: Division of Oncology Biostatistics and Bioinformatics, Johns Hopkins School of Medicine, Baltimore, MD, USA.
authors.forename: Elana J
authors.initials: EJ
authors.lastname: Fertig
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA.; Milton J. Dance Jr. Head and Neck Center, Greater Baltimore Medical Center, Baltimore, MD, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Califano
authors.affiliation: Department of Mathematics and Statistics, The College of New Jersey, Ewing, NJ, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Ochs
keywords: biomarkers; biostatistics; cancer; gene expression profiling