Systematic analysis of genes involved in oral cancer metastasis to lymph nodes

Xing’An Zhang,Kang Liu,Huadong Wang,Xiaoyao Tan,Lanfang Zhang,Xinsheng Han,Qiujiang Li,Gang Feng,Huawei Ming,Ying Lin

doi:10.1186/s11658-018-0120-2

Xing’An Zhang, Kang Liu + Show 8 more

Open Access

https://doi.org/10.1186/s11658-018-0120-2

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Abstract

Oral cancer remains a deadly disease worldwide. Lymph node metastasis and invasion is one of the causes of death from oral cancer. Elucidating the mechanism of oral cancer lymph node metastasis and identifying critical regulatory genes are important for the treatment of this disease. This study aimed to identify differentially expressed genes (gene signature) and pathways that contribute to oral cancer metastasis to lymph nodes. The GSE70604-associated study compared gene profiles in lymph nodes with metastasis of oral cancer to those of normal lymph nodes. The GSE2280-associated study compared gene profiles in primary tumor of oral cancer with lymph node metastasis to those in tumors without lymph node metastasis. There are 28 common differentially expressed genes (DEGs) showing consistent changes in both datasets in overlapping analysis. GO biological process and KEGG pathway analysis of these 28 DEGs identified the gene signature CCND1, JUN and SPP1, which are categorized as key regulatory genes involved in the focal adhesion pathway. Silencing expression of CCND1, JUN and SPP1 in the human oral cancer cell line OECM-1 confirmed that those genes play essential roles in oral cancer cell invasion. Analysis of clinical samples of oral cancer found a strong correlation of these genes with short survival, especially JUN expression associated with metastasis. Our study identified a unique gene signature – CCND1, JUN and SPP1 – which may be involved in oral cancer lymph node metastasis.

Highlights

Oral cancer is a major devastating head and neck cancer subtype and is any cancerous tissue growth located in the oral cavity or oropharynx [1]
Overlapping analysis was performed to identify common differentially expressed genes (DEGs) and pathways in these two studies. We focused on those 28 common DEGs that show consistent changes in both datasets and defined a “metastasis signature”: Cyclin D1 (CCND1), JUN and Secreted phosphoprotein 1 (SPP1) for oral cancer lymph node metastasis
In GSE70604, the comparisons of gene expression profiles were made between lymph nodes with metastasis of oral squamous cell carcinoma (OSCC) and normal lymph nodes

Summary

Introduction

Oral cancer is a major devastating head and neck cancer subtype and is any cancerous tissue growth located in the oral cavity or oropharynx [1]. There are several types of oral cancers, but around 90% of oral cancers are squamous cell carcinomas. Oral cancer is the sixth most common malignancy in humans. Its incidence and mortality have increased over the past decades. In 2013, oral cancer resulted in 135,000 deaths, up from 84,000 deaths in 1990 [2]. Oral cancer is characterized by poor prognosis and a low survival rate despite sophisticated surgical and radiotherapeutic modalities. The five-year survival rate is only 63% in the United States

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