Source: www.medpagetoday.com
Author: Chris Emery, Contributing Writer, MedPage Today

Researchers say they have identified dozens of microRNAs in saliva, raising hopes that saliva tests could assist in early detection of oral cancers.

Analyzing patient saliva with a polymerase chain reaction (PCR) technique, the researchers identified about 50 microRNAs — molecules that halt mRNA translation and/or lead to mRNA degradation, according to a report in the Sept. 1 edition of Clinical Cancer Research.

Of the miRNAs they found, a few were present at significantly lower levels in the saliva of patients with oral squamous cell carcinoma (OSCC) than in control subjects (P<0.05).

“Two of these miRNAs, miR-125a and miR-200a, are differentially expressed in the saliva of the OSCC patients compared with that of healthy controls,” David T. Wong, DMD, DMSc, of the Los Angeles School of Dentistry, and colleagues wrote.

“These findings suggest that the detection of miRNAs in saliva can be used as a noninvasive and rapid diagnostic tool for the diagnosis of oral cancer.”

The authors noted that OSCC is the sixth most common cancer in the U.S., accounting for 90% of oral cancers and leading to 8,000 deaths per year.

“The average five-year survival rate for OSCC is [about] 50%,” they wrote. “Shockingly, this number has not changed in last three decades. Therefore, an early detection method for OSCC is needed to increase long-term patient survival.”

Other recent studies have discovered hundreds of miRNAs in various organisms that play roles in cell growth, differentiation, apoptosis, stress response, immune response, and glucose secretion.

“Many research groups have shown that miRNAs are differentially expressed in various cancer cells compared with normal cells, and it seems that miRNAs more accurately cluster different types of solid tumors than mRNA, suggesting that miRNAs can be used to detect cancer,” the authors wrote.

Wong and his colleagues used reverse transcriptase-preamplification-quantitative PCR to test for the presence of 314 miRNAs in the saliva of 12 healthy subjects.

They found that 47 miRNAs were present in whole saliva and 52 were present in supernatant saliva. This suggested that a common set of miRNAs are detectable in human saliva.

The researchers then used RT-preamp-qPCR to test the levels of four miRNAs (miR-200a, miR-125a, miR-142-3p, miR-93) in a total 50 patients with oral squamous cell carcinoma and 50 healthy control patients (including the 12 original participants).

These miRNAs were early identified as being present at statistically significant levels between the smaller groups of 12 patients, and two of them, miR-125a and miR-200a, remained significantly different between the two groups of 50 participants.

“Together, these data suggest that miRNAs miR-200a and miR-125a are present at significantly lower levels in the saliva of OSCC patients,” the authors wrote.

The investigators also noted a paradox: miR-200a is overexpressed in oral squamous cell lines but reduced in saliva from patients with oral squamous cell cancer. They theorized that this could be due to miRNA being in a cell-free state in saliva but not in cell lines.

They concluded that the association between lower levels of the two miRNAs and oral cancer may provide a means of early cancer detection, and that the presence of miRNA adds a third type of molecule, in addition to proteome and transcriptome, that can be measured in human saliva.

Notes:
1. The study was funded by the National Institute of Dental and Craniofacial Research.
2. The authors reported no financial conflicts of interest.

Source reference:
Wong D, et al “Salivary microRNA: Discovery, characterization, and clinical utility for oral cancer detection” Clin Cancer Res 2009; 17: 5473-77.