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

Authors Zhao M, Ding L, Yang Y, Chen S, Zhu N, Fu Y, Ni Y, Wang Z

Received 15 July 2019

Accepted for publication 9 October 2019

Published 11 November 2019 Volume 2019:11 Pages 9553—9562

DOI https://doi.org/10.2147/CMAR.S223273

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly


Mengxiang Zhao,1,* Liang Ding,1,* Yan Yang,2 Sheng Chen,2 Nisha Zhu,1 Yong Fu,1 Yanhong Ni,1 Zhiyong Wang2

1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210093, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhiyong Wang
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, 30 Zhongyang Road, Nanjing 210008, Jiangsu, People’s Republic of China
Tel +86 137 709 2448
Email wangzhiyong67@163.com
Yanhong Ni
Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, People’s Republic of China
Tel +86 138 1451 6225
Email niyanhong12@163.com

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. 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.
Conclusion: Patients 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.

Keywords: PDCD4, eIF4A1, early-stage OSCC, prognosis, diagnosis


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