Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility.

Hon-Kit Lau,Shun-Fa Yang,Edie-Rosmin Wu,Mu-Kuan Chen,Lyu-Yao Wang,Ying-Erh Chou,Ming-Ju Hsieh,Pei-Yi Chu

doi:10.1371/journal.pone.0176246

Abstract

BackgroundOral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics.Methodology/Principal findingsReal-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node metastasis.ConclusionOur results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.

Highlights

Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies
Our results demonstrate that a joint effect of WNT1-inducible signaling pathway protein 1 (WISP1) rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC
WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC

Summary

Introduction

Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies. A previous study indicated that WISP1 enhances the migration of OSCC cells by increasing intercellular adhesion molecule-1 (ICAM-1) expression through the αvβ integrin receptor and apoptosis signal-regulating kinase 1 (ASK1), c-Jun N-terminal kinase (JNK)/p38, and activator protein-1 (AP-1) signal transduction pathways [15]. Oral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteinerich protein belonging to the Cyr, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics

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