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Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer

Author

Listed:
  • Ram Bhupal Reddy
  • Anupama Rajan Bhat
  • Bonney Lee James
  • Sindhu Valiyaveedan Govindan
  • Rohit Mathew
  • Ravindra DR
  • Naveen Hedne
  • Jeyaram Illiayaraja
  • Vikram Kekatpure
  • Samanta S Khora
  • Wesley Hicks
  • Pramila Tata
  • Moni A Kuriakose
  • Amritha Suresh

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

Suggested Citation

  • Ram Bhupal Reddy & Anupama Rajan Bhat & Bonney Lee James & Sindhu Valiyaveedan Govindan & Rohit Mathew & Ravindra DR & Naveen Hedne & Jeyaram Illiayaraja & Vikram Kekatpure & Samanta S Khora & Wesley , 2016. "Meta-Analyses of Microarray Datasets Identifies ANO1 and FADD as Prognostic Markers of Head and Neck Cancer," PLOS ONE, Public Library of Science, vol. 11(1), pages 1-21, January.
    • Handle: RePEc:plo:pone00:0147409
    DOI: 10.1371/journal.pone.0147409
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    References listed on IDEAS

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    1. Adaikalavan Ramasamy & Adrian Mondry & Chris C Holmes & Douglas G Altman, 2008. "Key Issues in Conducting a Meta-Analysis of Gene Expression Microarray Datasets," PLOS Medicine, Public Library of Science, vol. 5(9), pages 1-13, September.
    2. David Moher & Alessandro Liberati & Jennifer Tetzlaff & Douglas G Altman & The PRISMA Group, 2009. "Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-6, July.
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    1. Ram Bhupal Reddy & Samanta S Khora & Amritha Suresh, 2019. "Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach," PLOS ONE, Public Library of Science, vol. 14(7), pages 1-29, July.

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