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

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.

Investigation of an epidemic of Hepatitis E in Nellore in south India.

OBJECTIVE: To determine the incidence of acute hepatitis because of hepatitis E virus (HEV) and the source of the epidemic in Nellore in south India in 2008. METHODS: Anti-HEV IgM ELISA and RT-PCR for HEV-RNA were carried out on blood and stool samples from patients with acute hepatitis presenting to different hospitals in the city. The city was divided into 33 clusters, and 20 families from each cluster were systematically interviewed to determine the incidence of hepatitis E in the city. The survey was conducted on 2685 residents of 673 households from 24th November to 4th December 2008. RESULTS: The overall incidence of hepatitis was 5.7% (152/2685), i.e. an estimated 23,915 persons in the city were affected. There were two deaths because of acute hepatitis in the population surveyed translating to an estimated 315 deaths. Men had higher attack rates than women (7.8%vs. 3.5%) and young adults compared to children under 5 years (6.9%vs. 2.9%). Families drinking water from the pumping station at Bujjamarevu had the highest attack rate of 54.5% (39.8-69.2%). HEV IgM antibodies were present in 80/100 plasma samples tested. HEV-RNA was detected in 43/100 individuals tested, and isolates were characterized as genotype 1 by sequencing. CONCLUSION: Sewage draining into the river close to the pumping stations and broken pipelines crossing sewage drains may have triggered this large outbreak.

Genogroup IIb norovirus infections and association with enteric symptoms in a neonatal nursery in southern India.

Noroviruses (NoVs) are increasingly recognized as an important cause of acute gastroenteritis in children worldwide. However, there are limited data on the role of NoVs in neonatal infections and disease. The objectives of the present study were to determine the prevalence of NoVs in neonates with gastrointestinal disease using a case-control study design and to characterize the NoV strains infecting neonates. A total of 309 fecal samples from 161 neonates with gastrointestinal symptoms and 148 asymptomatic controls were screened for genogroup II (GII) NoV using reverse transcription-PCR. A subset of PCR-positive amplicons for the polymerase and capsid regions was sequenced. NoV was detected in 26.2% of samples, with the rate of detection being significantly higher among symptomatic neonates (60/161, 37.2%) than asymptomatic neonates (24/148, 14.1%) (P < 0.001). On the basis of sequencing of 29 strains, a single NoV strain, GIIb, was identified to be the predominant (27/29, 93.1%) cause of neonatal infections. Coinfection with rotavirus was seen in nearly one-third of symptomatic neonates. The study demonstrates a high prevalence of NoV infections in neonates and indicates that coinfection with rotavirus may result in significantly more gastrointestinal disease in this population.