title: Pathway Analysis using Gene-expression Profiles of HPV-positive and HPV-negative Oropharyngeal Cancer Patients in a Hispanic Population: Methodological Procedures.
abstract: OBJECTIVE
  The incidence of oral cavity and pharyngeal cancer in Puerto Rican men is higher than it is in the men of any other ethnic/racial group in the United States of America (US). The information regarding the effect of the human papilloma virus (HPV) in the gene-expression profile among patients with this cancer is limited in Hispanic community. We aim to describe the methodology for future studies to identify the molecular networks for determining overrepresented signaling and metabolic canonical pathways, based on the differential gene-expression profiles of HPV+ and HPV- samples from patients with oropharyngeal squamous cell carcinoma in Puerto Rico.
  
  
  METHODS
  We analyzed the RNA expression of 5 tissue samples from subjects diagnosed with oropharyngeal squamous cell carcinoma, 2 HPV+ and 3 HPV-, using Affymetrix GeneChips. The relative difference between the average gene expressions of the HPV+ and HPV- samples was assessed, based on the fold change (log2-scale).
  
  
  RESULTS
  Our analysis revealed 10 up regulated molecules (Mup1, LRP1, P14KA, ALYREF, and BHMT) and 5 down regulated ones (PSME4, KEAP1, ELK3, FAM186B, and PRELID1), at a cutoff of 1.5-fold change. Ingenuity Pathway Analysis showed the following biological functions to be affected in the HPV+ samples: cancer, hematological disease, and RNA post-transcriptional modification. QRT-PCR analysis confirmed only the differential regulation of ALYREF, KEAP1, and FAM186B genes.
  
  
  CONCLUSIONS
  The relevant methodological procedures described are sufficient to detect the most significant biological functions and pathways according to the HPV status in patients with oropharyngeal cancer in Puerto Rico.
authors.affiliation: Department of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
authors.forename: Erick
authors.initials: E
authors.lastname: Suárez
authors.affiliation: Puerto Rico Clinical and Translational Research Consortium, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
authors.forename: Lorena
authors.initials: L
authors.lastname: González
authors.affiliation: Center for Cranial Base, Head, and Neck Surgery, HIMA Health San Pablo Group, Caguas, PR; Department of Otolaryngology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
authors.forename: Carlos
authors.initials: C
authors.lastname: Pérez-Mitchell
authors.affiliation: Department of Biostatistics and Epidemiology, Graduate School of Public Health, University of Puerto Rico Medical Sciences Campus, San Juan, PR; University of Puerto Rico Comprehensive Cancer Center, San Juan, PR.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Ortiz
authors.affiliation: Cancer Center of HIMA Health San Pablo Group, Caguas, PR.
authors.forename: Maricarmen
authors.initials: M
authors.lastname: Ramírez-Sola
authors.affiliation: Center for Cranial Base, Head, and Neck Surgery, HIMA Health San Pablo Group, Caguas, PR.
authors.forename: Jaime
authors.initials: J
authors.lastname: Acosta
authors.affiliation: University of Puerto Rico Comprehensive Cancer Center, San Juan, PR; School of Health Professions, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
authors.forename: Raúl D
authors.initials: RD
authors.lastname: Bernabe-Dones
authors.affiliation: Department of Otolaryngology, School of Medicine, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
authors.forename: Carlos
authors.initials: C
authors.lastname: González-Aquino
authors.affiliation: Department of Chemistry, University of Puerto Rico Mayagüez Campus.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Montes-Rodríguez
authors.affiliation: Department of Biochemistry, School of Medicine and RCMI Center for Genomics in Health Disparities and Rare Diseases, University of Puerto Rico Medical Sciences Campus, San Juan, PR.
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Cadilla
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000821:virology; D011647:Puerto Rico; D012323:RNA Processing, Post-Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Gene expression; HPV; Microarrays; Network analysis; Oropharyngeal cancer; Puerto Rico