br Similar and dissimilar expression profiles of
Similar and dissimilar Chloramphenicol profiles of miRNAs in the saliva/WMF and serum/plasma of OSCC patients Several miRNAs are reported to show similar concentrations in different body fluids of OSCC patients. For example, miR-24, miR-146a, miR-184, miR-31, miR-451 and miR-26a have been reported to be mostly uniformly expressed both in the saliva/WMF and serum or plasma of OSCC patients compared to healthy controls (Table 3). The presence of these miRNAs in different body fluids as well as among different populations suggests that they can be used as biomarkers for oral cancer detection irrespective of their oral habits or environmental factors. Moreover, several miRNAs are also reported to be associated with cancer recurrence. The expression levels of these miRNAs pre- and post-surgery can thus be important biomarkers for cancer recurrence . On the contrary, certain miRNAs showed biphasic expression levels in different studies belonging to different population groups (Table 4). For example, miR-21 showed elevated levels in the saliva , serum , blood  and plasma [25,50] of OSCC patients from Japan, Netherlands, Germany and India compared to normal controls, but did not show any significant difference among OSCC patients of Taiwanese population . In another study with a Turkish population, miR-21 is reported to show lower levels in the plasma of patients having benign salivary tumors . This may be interpreted as the association of miR-21 specifically with malignant neoplasms. Similarly, miR-27b is reported to be elevated in the WMF of an American group of OSCC patients , but is found to be reduced in the plasma of OSCC patients from Taiwan . MiR-148a also showed a contradictory expression levels in the plasma of two different population cohorts , while it showed reduced levels in the WMF of OSCC patients . However, with this limited number of studies, it is difficult to ascertain their uniform or biphasic regulation across different body fluids. These miRNAs need to be validated among OSCC patients across different populations world-wide. Uniformity in sample collection, preparation and determination of expression profiles need to be standardized and reported in such biomarker studies to determine their reproducibility in other populations.
MiRNAs as prognostic biomarkers in oral cancer The expression patterns of certain miRNAs have shown positive correlation with clinical stage, lymph node metastasis and patient survival, indicating that these miRNAs can act as prognostic predictors in OSCC. Higher expression levels of miR-372 is shown to induce nodal metastasis and poor prognosis of oral carcinoma , while miR-134 showed association with number of metastases in HNSCC . MiR-146a is reported to show increased metastasis by down-regulating the expression of IRAK1, TRAF6 and NUMB . This, however, is contradicted by another study where overexpression of miR-146a was shown to inhibit invasion, tumorigenicity, and metastasis in OSCC cell lines by targeting SOX2 mRNA . Since, miR-146a is reported to show a biphasic expression, hence, deregulation of the downstream mRNAs needs to be analysed to comment on its prognostic and diagnostic potential in OSCC. Low expression of miR-150 in Esophageal Squamous Cell Carcinoma (ESCC) showed association with malignancy, such as tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and poor prognosis . MiR-338 is also a tumor suppressor miRNA in OSCC. It is reported to inhibit metastasis in hepatocellular carcinoma, lung cancer and gastric cancer as well [, , ]. Considering these observations, it could be proposed that an increased expression of miR-372 and miR-134, and a decreased expression of miR-150-5p and miR-338 might be a potential complex for detecting, and possibly predicting the risk of, metastasis in oral carcinoma (Fig. 1).