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. 2018 Sep 8;19(9):2664.
doi: 10.3390/ijms19092664.

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

Giuseppe Troiano  1 , Agostino Guida  2 , Gabriella Aquino  3 , Gerardo Botti  4 , Nunzia Simona Losito  5 , Silvana Papagerakis  6 , Maria Carmela Pedicillo  7 , Franco Ionna  8 , Francesco Longo  9 , Monica Cantile  10 , Antonio Pennella  11 , Lucio Lo Russo  12 , Giovanni Di Gioia  13 , Maria Addolorata Mariggiò  14 , Lorenzo Lo Muzio  15 , Giuseppe Pannone  16
Affiliations

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

Giuseppe Troiano et al. Int J Mol Sci. .

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.

Keywords: BIRC5; Survivin; TCGA; bioinformatic; immunohistochemistry; oral cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Analysis of previously published data comparing BIRC5 mRNA expression in cancer vs. non-cancer samples.
Figure 2
Figure 2
Analysis of OSCC patients included in the TCGA database by means of cBIOportal (http://www.cbioportal.org/) [32,33].
Figure 3
Figure 3
Network involved in the expression of the BIRC5 gene. Blue lines indicate genes controlling the state change of those genes to which the arrows are pointing; while the green lines indicate genes controlling the expression of those genes to which the arrows are pointing. Each gene is represented by a colored nucleus, indicating its overall alteration in the BIRC5 expression (the stronger the color intensity, the greater the alteration) surrounded by three areas: one filled with the color green, indicating how much the gene is mutated; the second one filled by both blue and red colors, indicating respectively the amount of homozygous deletion and the amplification of the gene; the third one filled by both pink and light blue colors, indicating respectively the upregulation and downregulation values of the gene. Where one or more areas are filled by grey and white stripes, data are missing.
Figure 4
Figure 4
Kaplan–Meier curves of overall survival for the immunohistochemical expression of (A) cytoplasmic or (B) nuclear cellular localization of Survivin in the authors’ own database.
Figure 5
Figure 5
Nuclear (A 10x, B 20x) and Cytoplasmic (C 4x, D 10x) expression of Survivin by IHC. Survivin was also expressed in cases showing aberrant mitosis (E 40x) and muscular invasion (F 4x).
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