Integrative Histologic and Bioinformatics Analysis of BIRC5/Survivin Expression in Oral Squamous Cell Carcinoma

Giuseppe Troiano,Silvana Papagerakis,Maria Mariggiò,Giovanni Di Gioia,Lucio Lo Russo,Franco Ionna,Lorenzo Lo Muzio,Francesco Longo,Gabriella Aquino,Maria Pedicillo,Antonio Pennella,Agostino Guida,Nunzia Losito,Giuseppe Pannone,Monica Cantile,Gerardo Botti

doi:10.3390/ijms19092664

Abstract

Survivin is a well-known protein involved in the inhibition of apoptosis in many different cancer types. The aim of this study was to perform an integrated bioinformatic and histologic analysis in order to study the expression and prognostic role of Survivin and its related gene BIRC5 in oral cancer. Publicly available databases were accessed via Gene Expression Omnibus and Oncomine, in addition raw data from The Cancer Genome Atlas (TCGA) were also obtained in order to analyze the rate of gene mutation, expression and methylation in patients with oral squamous cells carcinoma (OSCC). Immunohistochemistry (IHC) was also performed in order to evaluate the nuclear and cytoplasmic expression of Survivin and their correlation with cell proliferation in samples from OSCC patients. Results of this study revealed that Survivin is rarely mutated in OSCC samples and upregulated when compared to non-cancerous tissue. A negative correlation between the methylation of the island cg25986496 and BIRC5 mRNA expression was detected from TCGA data. IHC staining revealed that cytoplasmic (and not nuclear) expression of Survivin is associated with poor overall survival in OSCC patients, while the nuclear expression correlates with higher proliferation rate. In addition, data from TCGA database revealed that BIRC5 gene expression is an independent prognostic factor for OSCC patients.

Highlights

Over 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually worldwide [1]
It is encoded by the baculoviral IAP repeat containing 5 (BIRC5) gene located on the chromosome 17q25 [19].To our knowledge, only one meta-analysis has been previously published by pooling data from various studies evaluating the significance of Survivin as a prognostic factor in Oral squamous cell carcinoma (OSCC) patients
A direct comparison between these two databases (GSE10121 and GSE85195) was not possible, our comparative analysis indicated that the BIRC5 mRNA was upregulated in OSCC compared both to leukoplakia and oral normal tissue (Figure 1)

Summary

Introduction

Over 500,000 new cases of head and neck squamous cell carcinoma (HNSCC) are reported annually worldwide [1]. Oral squamous cell carcinoma (OSCC) is the most common subtype of HNSCC, accounting for more than 200,000 new cancer cases every year globally [3,4]. The etiology of OSCC is multifactorial; the most known risk factors are tobacco, excessive consumption of alcohol [10] and betel quid usage [11]: these factors can act separately or synergistically [12]. Other factors such as human papillomavirus (HPV) infection may be involved [13], especially in the oro-pharynx. Increasing evidence indicates that Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is an essential protein molecule for apoptotic inhibition and regulation of mitosis, but it plays a role in certain physiological processes, as well as in pathological conditions such as carcinogenesis in many human organs/cells [16,17]

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