title: Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer.
abstract: The head and neck squamous cell carcinoma (HNSCC) transcriptome has been profiled extensively, nevertheless, identifying biomarkers that are clinically relevant and thereby with translational benefit, has been a major challenge. The objective of this study was to use a meta-analysis based approach to catalog candidate biomarkers with high potential for clinical application in HNSCC. Data from publically available microarray series (N = 20) profiled using Agilent (4X44K G4112F) and Affymetrix (HGU133A, U133A_2, U133Plus 2) platforms was downloaded and analyzed in a platform/chip-specific manner (GeneSpring software v12.5, Agilent, USA). Principal Component Analysis (PCA) and clustering analysis was carried out iteratively for segregating outliers; 140 normal and 277 tumor samples from 15 series were included in the final analysis. The analyses identified 181 differentially expressed, concordant and statistically significant genes; STRING analysis revealed interactions between 122 of them, with two major gene clusters connected by multiple nodes (MYC, FOS and HSPA4). Validation in the HNSCC-specific database (N = 528) in The Cancer Genome Atlas (TCGA) identified a panel (ECT2, ANO1, TP63, FADD, EXT1, NCBP2) that was altered in 30% of the samples. Validation in treatment naïve (Group I; N = 12) and post treatment (Group II; N = 12) patients identified 8 genes significantly associated with the disease (Area under curve>0.6). Correlation with recurrence/re-recurrence showed ANO1 had highest efficacy (sensitivity: 0.8, specificity: 0.6) to predict failure in Group I. UBE2V2, PLAC8, FADD and TTK showed high sensitivity (1.00) in Group I while UBE2V2 and CRYM were highly sensitive (>0.8) in predicting re-recurrence in Group II. Further, TCGA analysis showed that ANO1 and FADD, located at 11q13, were co-expressed at transcript level and significantly associated with overall and disease-free survival (p<0.05). The meta-analysis approach adopted in this study has identified candidate markers correlated with disease outcome in HNSCC; further validation in a larger cohort of patients will establish their clinical relevance.
authors.affiliation: Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Division of Medical Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India.
authors.forename: Ram Bhupal
authors.initials: RB
authors.lastname: Reddy
authors.affiliation: Strand Life Sciences, Kirloskar Business Park, Bangalore, Karnataka, India.
authors.forename: Anupama Rajan
authors.initials: AR
authors.lastname: Bhat
authors.affiliation: Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Bonney Lee
authors.initials: BL
authors.lastname: James
authors.affiliation: Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Sindhu Valiyaveedan
authors.initials: SV
authors.lastname: Govindan
authors.affiliation: Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Rohit
authors.initials: R
authors.lastname: Mathew
authors.affiliation: Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: D R
authors.initials: DR
authors.lastname: Ravindra
authors.affiliation: Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Naveen
authors.initials: N
authors.lastname: Hedne
authors.affiliation: Department of Clinical Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Jeyaram
authors.initials: J
authors.lastname: Illiayaraja
authors.affiliation: Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Kekatpure
authors.affiliation: Division of Medical Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology University, Vellore, Tamil Nadu, India.
authors.forename: Samanta S
authors.initials: SS
authors.lastname: Khora
authors.affiliation: Department of Head and Neck/Plastic & Reconstructive Surgery, Roswell Park Cancer Institute, Buffalo, New York, United States of America.|Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Wesley
authors.initials: W
authors.lastname: Hicks
authors.affiliation: Strand Life Sciences, Kirloskar Business Park, Bangalore, Karnataka, India.
authors.forename: Pramila
authors.initials: P
authors.lastname: Tata
authors.affiliation: Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Mazumdar Shaw Medical Centre-Roswell Park Collaboration Program, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors.forename: Moni A
authors.initials: MA
authors.lastname: Kuriakose
authors.affiliation: Integrated Head and Neck Oncology Program, Mazumdar Shaw Centre for Translational Research, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.|Head and Neck Oncology, Mazumdar Shaw Medical Centre, Narayana Health, Bangalore, Karnataka, India.
authors.forename: Amritha
authors.initials: A
authors.lastname: Suresh
mesh_terms: D006801:Humans; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor / Q000378:metabolism; D018118:Chloride Channels / Q000235:genetics; D053200:Fas-Associated Death Domain Protein / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000473:pathology; D000090803:mu-Crystallins; D009363:Neoplasm Proteins / Q000235:genetics; D011379:Prognosis
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor; D018118:Chloride Channels; C000716469:CRYM protein, human; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D000090803:mu-Crystallins; D009363:Neoplasm Proteins