Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) association with lymph node metastasis predicts poor survival in oral squamous cell carcinoma patients.

Bharath Kumar Velmurugan,Ming-Hsui Tsai,Chun-Hung Hua,Kun-Tu Yeh,Mei-Chung Chin,Ying-Chin Ko,Shang-Lun Chiang,Jan-Gowth Chang,Shu-Hui Lin,Chien-Hung Lee,Zhi-Hong Wang

doi:10.18632/oncotarget.7681

Abstract

Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) is a multifunctional protein aberrantly expressed in various types of cancers. However, its expression pattern and clinical significance in oral squamous cell carcinoma (OSCC) remains unclear. In this study, we immunohistochemically investigated the expression pattern of ANP32A in 259 OSCC patients and the results were correlated with clinicopathological factors using Allred, Klein and Immunoreactive scoring (IRS) system. Our data indicated that high expression of ANP32A was significantly associated with N stage and tumor differentiation status in OSCC patients. High ANP32A expression with N2/N3 stage had an increased mortality risk than low ANP32A expressing OSCC patients with N0/N1 stage. Functional studies revealed that knockdown of ANP32A significantly decreased the migration and invasion ability thereby concomitantly increasing E-cadherin and decreasing Slug, Claudin-1 and Vimentin expression in vitro. These results suggest that ANP32A is commonly increased in oral squamous cell carcinoma and ANP32A protein could act as a potential biomarker for prognosis assessment of oral cancer patients with lymph node metastasis.

Highlights

Oral squamous cell carcinoma (OSCC) is the sixth leading cause of cancer death in the worldwide (The agestandardized per 100,000 GLOBOCAN 2008, IARC); in Taiwan more than 6500 new cases of oral and pharyngeal cancer are diagnosed annually (7-8% of all cancers) [1]
To study the prevalence of Acidic leucine rich nuclear phosphoprotein32A (ANP32A) in OSCC patients, at first we examined the expression pattern of ANP32A using immunohistochemistry on the tumor tissues and adjacent non-tumor tissues from 259 patients with OSCC (Figure 1)
Because ANP32A expression was associated with lymph node metastasis and tumor differentiation, we further evaluated the joint effect of ANP32A expression and the two pathological factors on mortality

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the sixth leading cause of cancer death in the worldwide (The agestandardized per 100,000 GLOBOCAN 2008, IARC); in Taiwan more than 6500 new cases of oral and pharyngeal cancer are diagnosed annually (7-8% of all cancers) [1]. It is of important to identify the molecular markers that are associated with OSCC malignancy; which may further improve the clinical management and therapeutic development [5, 6]. In pancreatic adenocarcinoma expression of ANP32A was well correlated with their differentiation status. This well differentiated tumors showed normal expression of ANP32A, whereas reduced or absent in poorly differentiated tumors [13]. Most of the studies have found that, ANP32A function as a tumor suppressor protein [9, 14], surprisingly increased expression was found in hepatocellular carcinoma[15], colorectal cancer[16], pancreatic tumor[17] and liver cancer [15]. Whether the aberrant expression of ANP32A in OSCC is associated with malignancy, metastasis, or prognosis remains unknown

Methods

Results

Conclusion