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

Abstract

BackgroundProgrammed 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.MethodsImmunohistochemical 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.ResultsWe 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. PDCD4TCs was negative associated with eIF4A1TCs in tumor center, and patients with low PDCD4TCs or high eIF4A1TCs had poorer differentiation. Moreover, aberrant PDCD4/eIF4A1 signal led to higher Ki-67 level. Interestingly, patients with low expressed PDCD4TILs had better prognosis, indicating the function heterogeneity of PDCD4 in different cell types. Furthermore, low PDCD4 TCs and high eIF4A1TCs predicted higher postoperative recurrence rate and are significant independent risk factors for early-stage OSCC.ConclusionPatients with low PDCD4TCs and high eIF4A1TCs have higher recurrence rate and poor clinical outcome. Of note, PDCD4TILs exerts contradictory function. Thus, PDCD4/eIF4A1 targeting therapeutics should consider the function heterogeneity of PDCD4.

Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers

“…Similarly, the silencing of eIF4A1 in WM858 cells significantly decreases melanoma proliferation and invasion (Joyce et al, 2017). eIF4A1 has also been shown to promote the tumor cell malignant phenotype in breast (Modelska et al, 2015b), oral squamous cell (Zhao et al, 2019), and cervical (Liang et al, 2017) cancers.…”

The Hidden Treasures of Preoperative Blood Assessment in Oral Cancer: A Potential Source of Biomarkers

“…Ideally, these biomarkers should be available as early as possible, even from the moment of diagnosis, and should be cost efficient for worldwide implementation, providing the advantage of optimal risk stratification and therapy selection before the initiation of any treatment. A wide variety of molecules that meet the criteria for biomarkers was investigated in scientific research conducted on OSCC; however, they were not introduced in standard clinical care due to the challenges raised by costs, the necessity of specific equipment, and specially trained personal [8][9][10][11][12].…”

Lipid Droplet-Related PLIN2 in CD68+ Tumor-Associated Macrophage of Oral Squamous Cell Carcinoma: Implications for Cancer Prognosis and Immunotherapy

“…The protocol of IHC of formalin-fixed paraffin-embedded sections was performed as previously described ( 19 ). Anti-PLIN2 (ab181452, Abcam, Waltham, MA, USA) was used at a dilution ratio of 1:300, and the serial sections were incubated with primary antibodies such as anti-CD4 (ZSGB-BIO, ZM-0418), anti-CD8 (ZSGB-BIO, ZA-0508), anti-CD19 (ZSGB-BIO, ZM-0038), anti-CD56 (ZSGB-BIO, ZM-0057), anti-CD68 (ZSGB-BIO, ZM-0464), and anti-FOXP3 (ab253297, Abcam).…”