Aberrant Expression Of PDCD4/eIF4A1 Signal Predicts Postoperative Recurrence For Early-Stage Oral Squamous Cell Carcinoma

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.