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.

Oncogenic drivers in 11q13 associated with prognosis and response to therapy in advanced oropharyngeal carcinomas

“…A meta-analysis comprising 15 publically available microarray gene expression data assessing 140 normal and 277 HNSCC samples revealed a list of 181 differentially expressed genes. ANO1 and FADD (both mapped in 11q13) were overexpressed in at least 30% of the TCGA samples (528 HNSCC), and associated with higher risk of recurrence and death [46]. Gains of 11q13.2, including CPT1A, were also associated with worse survival in patients with esophageal carcinoma [47].…”

Molecular prognosticators in clinically and pathologically distinct cohorts of head and neck squamous cell carcinoma—A meta-analysis approach

“…A comparison across the different sites indicated that 698 genes were common across all the 3 sites (S2 File). The significant gene entities from each site, when cross compared with the previously published database of 181 gene entities (up regulated: 168; down regulated: 13) [21] indicated that 66.3% (n = 119/181) of the genes in the database were identified in tongue cancer, while 109/181 genes (60.22%) were common with laryngopharyngeal subset and 95/181 genes (52.48%) were common with oropharyngeal cancer.…”

Galectin-3 Is Implicated in Tumor Progression and Resistance to Anti-androgen Drug Through Regulation of Androgen Receptor Signaling in Prostate Cancer

“…The scanned images were analyzed with Feature Extraction Software 10.7 (Agilent) using default parameters (protocol GE1-107_Sep09 and Grid: 072363_D_F_ 20150612). The microarray data across all chips and genes were analyzed using GeneSpring (version 13.0) and normalized by 75 percentile shift (25,26).…”