Prognostic value and targeted inhibition of survivin expression in esophageal adenocarcinoma and cancer-adjacent squamous epithelium

Malhotra, U and Zaidi, AH and Kosovec, JE and Kasi, PM and Komatsu, Y and Rotoloni, CL and Davison, JM and Irvin, CR and Hoppo, T and Nason, KS and Kelly, LA and Gibson, MK and Jobe, BA (2013) Prognostic value and targeted inhibition of survivin expression in esophageal adenocarcinoma and cancer-adjacent squamous epithelium. PLoS ONE, 8 (11).

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Abstract

Background: Survivin is an inhibitor of apoptosis and its over expression is associated with poor prognosis in several malignancies. While several studies have analyzed survivin expression in esophageal squamous cell carcinoma, few have focused on esophageal adenocarcinoma (EAC) and/or cancer-adjacent squamous epithelium (CASE). The purpose of this study was 1) to determine the degree of survivin up regulation in samples of EAC and CASE, 2) to evaluate if survivin expression in EAC and CASE correlates with recurrence and/or death, and 3) to examine the effect of survivin inhibition on apoptosis in EAC cells. Methods: Fresh frozen samples of EAC and CASE from the same patient were used for qRT-PCR and Western blot analysis, and formalin-fixed, paraffin-embedded tissue was used for immunohistochemistry. EAC cell lines, OE19 and OE33, were transfected with small interfering RNAs (siRNAs) to knockdown survivin expression. This was confirmed by qRT-PCR for survivin expression and Western blot analysis of cleaved PARP, cleaved caspase 3 and survivin. Survivin expression data was correlated with clinical outcome. Results: Survivin expression was significantly higher in EAC tumor samples compared to the CASE from the same patient. Patients with high expression of survivin in EAC tumor had an increased risk of death. Survivin expression was also noted in CASE and correlated with increased risk of distant recurrence. Cell line evaluation demonstrated that inhibition of survivin resulted in an increase in apoptosis. Conclusion: Higher expression of survivin in tumor tissue was associated with increased risk of death; while survivin expression in CASE was a superior predictor of recurrence. Inhibition of survivin in EAC cell lines further showed increased apoptosis, supporting the potential benefits of therapeutic strategies targeted to this marker. © 2013 Malhotra et al.

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Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Malhotra, U Zaidi, AH Kosovec, JE Kasi, PM Komatsu, Y Rotoloni, CL Davison, JM jmd91@pitt.edu JMD91 Irvin, CR Hoppo, T Nason, KS ksn7@pitt.edu KSN7 Kelly, LA Gibson, MK Jobe, BA
Date:	4 November 2013
Date Type:	Publication
Journal or Publication Title:	PLoS ONE
Volume:	8
Number:	11
DOI or Unique Handle:	10.1371/journal.pone.0078343
Schools and Programs:	School of Medicine > Pathology School of Medicine > Cardiothoracic Surgery
Refereed:	Yes
Date Deposited:	30 Jan 2014 17:33
Last Modified:	27 Jan 2019 03:55
URI:	http://d-scholarship.pitt.edu/id/eprint/20370

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