Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis.

To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from Bri2, were significantly associated with patients having cerebellar dysfunction and cognition impairment. Furthermore, expression levels of Bri2 were specifically decreased in the cerebellum compared to other areas of same brain in MS but not in controls, suggesting that decreased cerebellar Bri2 expression may play a role in cerebellar dysfunction. The association with cognition impairment is also of interest because Bri2 is linked to the amyloid processing pathway in the brain. CSF levels of Bri2-23 may serve as a biomarker of these functions in MS and merits further investigation.

Genomic analysis to define molecular basis of aggressiveness in a mouse model of oral cancer.

To investigate the molecular basis underlying aggressive behavior in oral squamous cell carcinoma (OSCC), our laboratory developed a carcinogen-induced mouse oral cancer (MOC) cell line model that encompasses the growth and metastasis spectrum of its human counterpart. We performed next-generation sequencing (NGS) and gene expression microarray profiles to explore the genomic and transcriptional backgrounds of the differential MOC line phenotypes, as well as, the cross-species relevance of the model. Here we describe the comparative analysis of NGS (www.ncbi.nlm.nih.gov/biosample?LinkName=bioproject_biosample_all&from_uid=247825) and expression microarray (www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50041) data from the MOC lines and corresponding human data, as described in our recent publication [1].

Pediatric quality of life in children with otolaryngologic disease: what inventories are available and what is still needed?

PURPOSE OF REVIEW: Quality of life (QOL) is an important patient-oriented outcome in common disorders, particularly when one management strategy is not clearly superior to an alternative. This article reviews the recently published literature that evaluated QOL in children with common pediatric otolaryngologic problems. RECENT FINDINGS: Among the 41 reviewed articles that used QOL as an outcome, 14 disease-specific QOL surveys and 12 generic QOL questionnaires were used. QOL instruments that had been validated in adults were frequently used in children without validation in pediatric populations. For children, parent-reported outcomes of caregiver concerns are often used as proxy measures of QOL for the child, and only a few QOL instruments asked the child to rate their own perception of their QOL. Several studies used nonvalidated QOL surveys as outcomes. SUMMARY: QOL is being evaluated in an increasing number of pediatric otolaryngologic disorders. Although there are numerous surveys to measure generic pediatric QOL, validated disease-specific surveys for children are less common, especially those that utilize child self-report. The lack of disease-specific pediatric surveys for otolaryngologic disorders hampers the ability to document change or differences in patient-oriented outcomes with interventions.

A surprising cross-species conservation in the genomic landscape of mouse and human oral cancer identifies a transcriptional signature predicting metastatic disease.

PURPOSE: Improved understanding of the molecular basis underlying oral squamous cell carcinoma (OSCC) aggressive growth has significant clinical implications. Herein, cross-species genomic comparison of carcinogen-induced murine and human OSCCs with indolent or metastatic growth yielded results with surprising translational relevance. EXPERIMENTAL DESIGN: Murine OSCC cell lines were subjected to next-generation sequencing (NGS) to define their mutational landscape, to define novel candidate cancer genes, and to assess for parallels with known drivers in human OSCC. Expression arrays identified a mouse metastasis signature, and we assessed its representation in four independent human datasets comprising 324 patients using weighted voting and gene set enrichment analysis. Kaplan-Meier analysis and multivariate Cox proportional hazards modeling were used to stratify outcomes. A quantitative real-time PCR assay based on the mouse signature coupled to a machine-learning algorithm was developed and used to stratify an independent set of 31 patients with respect to metastatic lymphadenopathy. RESULTS: NGS revealed conservation of human driver pathway mutations in mouse OSCC, including in Trp53, mitogen-activated protein kinase, phosphoinositide 3-kinase, NOTCH, JAK/STAT, and Fat1-4. Moreover, comparative analysis between The Cancer Genome Atlas and mouse samples defined AKAP9, MED12L, and MYH6 as novel putative cancer genes. Expression analysis identified a transcriptional signature predicting aggressiveness and clinical outcomes, which were validated in four independent human OSCC datasets. Finally, we harnessed the translational potential of this signature by creating a clinically feasible assay that stratified patients with OSCC with a 93.5% accuracy. CONCLUSIONS: These data demonstrate surprising cross-species genomic conservation that has translational relevance for human oral squamous cell cancer. Clin Cancer Res; 20(11); 2873-84. ©2014 AACR.