Genomewide Study of Salivary MicroRNAs for Detection of Oral Cancer.

MicroRNAs (miRNAs) in human saliva have recently demonstrated to be potential biomarkers for diagnosis purposes. However, lack of well-characterized/matched clinical groups and lack of suitable endogenous control (EC) for salivary extracellular miRNA detection and normalization are among the restrictions of applying salivary-based miRNA biomarker discovery. In the present study, we examined the differential expression pattern of miRNAs among 4 groups of subjects-including patients with oral squamous cell carcinoma (OSCC), patients with OSCC in remission (OSCC-R), patients with oral lichen planus, and healthy controls (HCs)-using a genomewide high-throughput miRNA microarray. First, we systematically screened 10 pooling samples and 34 individual samples of different groups to find a proper EC miRNA. We then investigated the genomewide expression patterns of differentially expressed miRNAs in saliva of different groups using NanoString nCounter miRNA expression assay and real-time quantitative polymerase chain reaction, followed by construction of receiver operating characteristic curves to determine the sensitivity and specificity of the assay. We identified miRNA-191 as a suitable EC miRNA with minimal intergroup and intragroup variability, and we used it for normalization. Of more than 700 miRNAs tested, 13 were identified as being significantly deregulated in saliva of OSCC patients compared to HCs: 11 miRNAs were underexpressed (miRNA-136, miRNA-147, miRNA-1250, miRNA-148a, miRNA-632, miRNA-646, miRNA668, miRNA-877, miRNA-503, miRNA-220a, miRNA-323-5p), and 2 miRNAs were overexpressed (miRNA-24, miRNA-27b). MiRNA-136 was underexpressed in both OSCC vs. HCs and OSCC vs. OSCC-R. MiRNA-27b levels were significantly higher in OSCC patients compared to those found in HCs, patients with OSCC-R, and patients with oral lichen planus and served as a characteristic biomarker of OSCC. Receiver operating characteristic curve analyses showed that miRNA-27b could be a valuable biomarker for distinguishing OSCC patients from the other groups. Our novel findings established a reliable EC miRNA for salivary-based diagnostic and indicate that the salivary miRNA profiles are discriminatory in OSCC patients.

Bioinformatics construction of the human cell surfaceome.

Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.

Overview of bioinformatics and its application to oral genomics.

The "informatics revolution" in both bioinformatics and dental informatics will eventually change the way we practice dentistry. This convergence will play a pivotal role in creating a bridge of opportunity by integrating scientific and clinical specialties to promote the advances in treatment, risk assessment, diagnosis, therapeutics, and oral health-care outcome. Bioinformatics has been an emerging field in the biomedical research community and has been gaining momentum in dental medicine. This area has created a steady stream of large and complex genomic data, which has transformed the way a clinical or basic science researcher approaches genomic research. This application to dental medicine, termed "oral genomics", can aid in the molecular understanding of the genes and proteins, their interactions, pathways, and networks that are responsible for the development and progression of oral diseases and disorders. As the result of the Human Genome Project, new advances have prompted high-throughput technologies, such as DNA microarrays, which have become accepted tools in the biomedical research community. This manuscript reviews the two most commonly used microarray technologies, basic microarray data analysis, and the results from several ongoing oral cancer genomic studies.

Associations between gene expressions in breast cancer and patient survival.

We analyzed associations between gene expression in breast cancer and patient survival for 8024 genes from a previously published microarray data set. Analysis of survival, by using the logrank test, was performed automatically for each gene. After correcting for multiple testing, we identified 95 genes whose expression was significantly associated with patient survival. The independent prognostic value of the genes ranking the highest in univariate analysis, together with clinical parameters, was assessed by Cox multivariate regression analysis. The P-values from these logrank tests were also mapped to chromosomal positions and compared with previously reported amplicon regions. We used PubGene web tools to identify groups of genes that had co-occurred in the literature and whose expression patterns were associated with survival. Our analyses demonstrate the comprehensiveness of the microarray technology with respect to measuring gene expression and indicate that the technology may be used to screen for potential clinical markers.

Locally aggressive solitary fibrous tumor in the infraorbital region: a case report and review of the literature.

We describe a case of a soft tissue neoplasm in the infraorbital region of a 31-year-old African-American man that met histologic and immunohistochemical criteria for solitary fibrous tumor. This uncommon spindle cell neoplasm was first described in the pleura, but it has since been reported in many other soft tissue locations. The lesion was locally aggressive and successfully treated by local excision. Solitary fibrous tumor can be locally destructive and can occur in a wide variety of tissues or organs; this is the seventh published case of solitary fibrous tumor in the orofacial region.