Exploring the role of survivin in neuroendocrine neoplasms
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Ahmad Hanif1, Sunyoung Lee1, Medhavi Gupta1, Ankush Chander2, Eric D. Kannisto3, Achamaporn Punnanitinont4, Robert Fenstermaker5, Michael Ciesielski5, Kristopher Attwood3, Jingxin Qiu2, Sai Yendamuri4 and Renuka Iyer1
1 Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
2 Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
3 Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
4 Department of Thoracic Surgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
5 Department of Neurosurgery, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA
Keywords: neuroendocrine tumors; survivin; immunohistochemistry; biomarkers; radiosensitivity
Received: February 06, 2020 Accepted: May 14, 2020 Published: June 09, 2020
Neuroendocrine tumors (NETs) are a heterogenous group of tumors. While most NETs have excellent prognosis, certain subsets have aggressive biology and have limited treatment options. We explored the role of survivin in NET as a prognostic and potentially therapeutic marker. Tissue microarrays of 132 patients were stained for survivin using immunohistochemistry (IHC) and correlated with outcomes. Using genomic database, we then correlated survivin (BIRC5) mRNA expression with radiosensitivity index (RSI) in 52 samples of NET. Finally, we studied the effect of radiation on survivin expression in human cell lines and the impact of knock-down of BIRC5 on cell proliferation and radiation sensitivity. We found that survivin positivity by IHC correlated with a shorter survival (overall survival 8.5 years vs. 18.3 years, p < 0.001). There was a positive correlation between BIRC5 expression and RSI (r = 0.234, p < 0.0001). Radiation exposure increased BIRC5 gene expression in a human carcinoid cell line. Knockout of BIRC5 using siRNA reduced proliferation of neuroendocrine cells but did not increase radiation sensitivity. We conclude that survivin expression in NET correlates with an inferior survival and survivin expression in human carcinoid cell lines increases after exposure to ionizing radiation.
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