Abstract

The clinical significance and biological function of DEXD/H box helicase 60 (DDX60) in oral cancer remains unknown. Herein, we evaluated the association of DDX60 expression with tumorigenesis and the prognosis of oral squamous cell carcinoma (OSCC). DDX60 expression was examined by immunohistochemistry on tissue microarray slides of 494 OSCC patients, including 180 buccal mucosal SCC (BMSCC), 241 tongue SCC (TSCC), and 73 lip SCC (LSCC) patients. DDX60 expression was significantly increased in all three subsites of OSCC compared to its expression in tumor adjacent normal tissues. However, its association with tumorigenesis was specific to the oral cavity subsite after the stratification of betel quid chewing, smoking, and drinking. Among OSCC patients, higher levels of DDX60 expression were associated with the male gender, a well-differentiated tumor, advanced stage of disease, and a large tumor size with subsite specific features. LSCC patients with high DDX60 expression levels showed shorter disease-specific survival, particularly those with moderately or poorly differentiated tumors. Additionally, TSCC or OSCC patients with high DDX60 expression showed a poor disease-free survival (DFS), particularly those with moderately or poorly differentiated tumors. Therefore, DDX60 is a novel and unfavorable biomarker for tumorigenesis and prognosis of OSCC in a subsite-specific manner.

Highlights

  • DEAD-box (DDX) proteins, distinguished by the presence of a conserved amino-acid sequence AspGlu-Ala-Asp motif, are the largest family of RNA helicases, with 37 members in humans [1]

  • These results indicated that DDX60 may be involved in the tumorigenesis of oral squamous cell carcinoma (OSCC)

  • These results revealed that DDX60 expression may be correlated with tumorigenesis in OSCC, and its expression was quite different between the three different subsites of the oral cavity

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Summary

Introduction

DEAD-box (DDX) proteins, distinguished by the presence of a conserved amino-acid sequence AspGlu-Ala-Asp motif, are the largest family of RNA helicases, with 37 members in humans [1]. DDX60, a novel DEAD box RNA helicase, is induced after a virus infection. The helicase domain of DDX60 binds to viral RNA and DNA, and its ATP-binding site is essential for DDX60-activated RIG, leading to type I interferon (IFN) expression [1113]. DDX60 and its highly similar homolog DEAD box polypeptide 60-like (DDX60L) have recently been described as interferon-stimulated products upon a viral infection. DDX60L plays a distinct and specific function in restricting hepatitis C virus replication [14]. DDX60 is involved in protection against viral infections, the clinical significance and biological function of DDX60 in cancers, oral cancer, remain largely unknown

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