Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients

Abstract

Phosphatidylinositol-3-kinases are kinases that lead to AKT phosphorylation and thus mTOR and GSK3β activation. These proteins are linked to tumorigenesis, but their roles in driving cervical lymph node (CLN) metastasis of oral squamous cell carcinoma (OSCC) cells are unknown. This study aimed to investigate the role of AKT, mTOR, and GSK3β proteins in the occurrence of CLN metastasis in OSCC patients. Ninety and 18 paraffin-embedded OSCC and oral mucosa samples were included, respectively. We divided our OSCC patients into non-metastasizing (PNM) and metastasizing (PM) groups, and the expression of total AKT, pAKT1^Thr308, pAKT^Ser473, GSK3β, pGSK3β^Ser9, and pmTOR^Ser2448 was analyzed by immunohistochemistry. The mean expression of GSK3β, pGSK3β^Ser9, total AKT, and pmTOR²⁴⁴⁸ was always higher in the OSCC tissues than that in the controls. A positive correlation was also found among these proteins. Total AKT, pmTOR^Ser2448, and pGSK3β^Ser9 expression was significantly higher in the PNM and PM groups than that in the control group. However, only GSK3β expression was significantly higher in the PM group compared with the PNM group. High expression levels of GSK3β and pGSK3β^Ser9 were significantly associated with CLN metastasis, but only GSK3β remained an independent predictor of CLN metastasis. pGSK3β^Ser9 and CLN metastasis were associated with a poor prognosis, but only the latter remained an independent prognostic parameter. Kaplan-Meier survival curves showed that pGSK3β^Ser9 and CLN metastasis were significantly related to reduced survival rates. These results suggest that AKT and mTOR proteins are involved in OSCC biology and that GSK3β itself may drive CLN metastatic spread of OSCC cells.

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