Background: Programmed cell death 4 (PDCD4 ) as a tumor suppressor gene inhibits growth and metastasis of cancer cells, which involved with eIF4A1, the inhibitor of translation initiation. Although the prognosis of early-stage oral squamous cell carcinoma (OSCC) is generally better, but many patients occur recurrence after surgery. Understanding the clinical expression pattern of PDCD4/eIF4A1 signal would provide diagnostic biomarker and target therapy premise for early-stage OSCC patients.
Methods: Immunohistochemical analysis was performed on 69 early-stage (T1/2N0M0) OSCC samples to evaluate temporal expression and prognostic value of eIF4A1 and PDCD4 in early-stage OSCC according to cell types and microlocalization. The correlations between PDCD4/eIF4A1 signal and Ki-67, postoperative recurrence and metastasis were determined.
Results: We found that PDCD4 was presented in tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) but absent in fibroblast-like cells (FLCs). eIF4A1 was only presented in TCs. PDCD4^TCs was negative associated with eIF4A1^TCs in tumor center, and patients with low PDCD4^TCs or high eIF4A1^TCs had poorer differentiation. Moreover, aberrant PDCD4/eIF4A1 signal led to higher Ki-67 level. Interestingly, patients with low expressed PDCD4^TILs had better prognosis, indicating the function heterogeneity of PDCD4 in different cell types. Furthermore, low PDCD4 ^TCs and high eIF4A1^TCs predicted higher postoperative recurrence rate and are significant independent risk factors for early-stage OSCC.
Conclusion: Patients with low PDCD4^TCs and high eIF4A1^TCs have higher recurrence rate and poor clinical outcome. Of note, PDCD4^TILs exerts contradictory function. Thus, PDCD4/eIF4A1 targeting therapeutics should consider the function heterogeneity of PDCD4.
Keywords: PDCD4, eIF4A1, early-stage OSCC, prognosis, diagnosis