Previous studies have demonstrated localization of miR stain
Previous studies have demonstrated localization of miR-21 staining in stromal Exendin-3 (9-39) amide of OSCC associated with the tongue and mouth floor—this might be a useful prognostic predictor. We also observed miR-21 staining in the stromal cells of tumors. However, since multiple lines of evidence indicate the involvement of miR-21 in the aggressiveness of OSCC, our approach has rather focused on studying the epithelial tumor cells. We have been able to show that there is modest miR-21 staining in the tumor cell component of OSCC, and that this activity is involved in modulating cell migration in OSCC cells. It seems likely that the discrepancies among oral sites, in the clinical stage of the tumor and in the race of the patient, may underlie the differences in stromal miR-21 staining that occur across different study subsets.
Decreased expression of PTEN is an indicator of a poor prognosis in many cancers, including colorectal cancer, prostate cancer, and breast cancer. A deficiency of PTEN expression is also a poorly prognostic factor for OSCC. As miR-21 targets multiple oncogenic events, including PTEN, during pathogenesis, and because PTEN is an inhibitor of the activator PI3K/AKT/S6 pathway, our study was able to show a reverse association between miR-21 expression and PTEN expression. Nevertheless, our analysis also showed high immunoreactivity for phosphor-S6 across all OSCC samples in this cohort, even in tumors with medium PTEN immunoreactivity. Similar ambiguity is found in other studies. Therefore, this study is unable to link PNI to the PI3K/AKT pathway. Our results seem to imply that, although miR-21-PTEN cascade may reinforce OSCC cells with a PNI propensity, the PI3K/AKT/S6 pathway does not seem to be the single factor involved in causing PNI in OSCC. These findings are in agreement with a previous investigation of PNI associated with pancreatic carcinoma.
In conclusion, this study provides a new line of evidence demonstrating that there is an association between miR-21-PTEN disregulation and PNI in OSCC. miR-21 is an independent factor associated with disease-free survival in OSCC. High miR-21 expression is able to predict worse prognosis among OSCC patients. Our data also hint that miR-21 expression may be an indicator of PNI-positive and more aggressive treatment may be of benefit to the OSCC patient without PNI in the surgical specimen.
Acknowledgments This study was supported by a grant (YMUH 2014-013) from National Yang-Ming University Hospital.