High Vimentin Expression Associated with Lymph Node Metastasis and Predicated a Poor Prognosis in Oral Squamous Cell Carcinoma.

Shuli Liu,Zhiyuan Zhang,Dongxia Ye,Hanguang Zhu,Wenzheng Guo,Dongliang Xu,Jiong Deng,Yueling Liao,Weimin Ye,Ling Zhang,Hongyong Song,Tong Wang,Liu Liu

doi:10.1038/srep38834

Abstract

Oral squamous cell carcinoma (OSCC) is a common public health problem worldwide with poor prognosis, which is largely due to lymph node metastasis and recurrence. Identification of specific molecular markers of OSCC with lymph node metastasis would be very important for early and specific diagnosis. In this study, we screened for the potential prognosis markers via unbiased transcriptomic microarray analysis in paired two OSCC cell lines, a lymph node metastatic HN12 cell line and a low metastatic parental HN4 cell line. The results showed that vimentin, with 87-fold increase of expression, was on the top of all upregulated genes in metastatic HN12 cells compared to non-metastatic HN4 cells. Treatment of non-metastatic HN4 cells with TGF-β1 induced epithelial to mesenchymal transition (EMT), with increased vimentin expression as well as enhanced migration activity. Consistently, knockdown of vimentin via siRNA resulted in suppressed invasion and migration activities of HN12 cells, suggesting an essential role of vimentin in EMT-related functions of OSCC cells. Finally, immunohistochemical (IHC) staining analysis showed that high vimentin expression was strongly associated with high lymph node metastases (p < 0.05), and poor overall survival (p < 0.05) in OSCC patients. Thus, high vimentin expression is strongly associated with increased metastatic potential, and may serve as a prediction marker for poor prognosis in OSCC patients.

Highlights

Epithelial and mesenchymal transition (EMT) has been shown to play a critical role in tumor invasion and metastasis
We have identified vimentin as a promising prognosis marker for metastatic Oral squamous cell carcinoma (OSCC)
Vimentin upregulation is on the top of the genes that are differentially expressed in metastatic versus non-metastatic OSCC cells

Summary

Introduction

Epithelial and mesenchymal transition (EMT) has been shown to play a critical role in tumor invasion and metastasis. The functional link and the pathological role of vimentin expression in OSCC cells have not been defined. It is still unclear whether vimentin could serve as a good candidate prognosis marker for metastatic OSCC. We hypothesized that genes differentially expressed in these two OSCC cell lines may be responsible for the difference of their metastatic potential, and may serve as a potential marker for predication of lymph node metastasis and patient prognosis. OSCC patients with vimentin positive staining have high risk for cervical lymph node metastastic potential and should be aggressively treated in clinic

Methods

Results

Conclusion