Constitutive expression of c-REL in uveal melanoma patients: correlation with clinicopathological parameters and patient outcome
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Uveal melanoma (UM) is the most common intraocular cancer with a high mortality rate that requires new research in the field of prevention and treatment. c-REL is a member of the nuclear factor κB (NF-κB) transcription factor family and an emerging regulator of tumorigenesis. Therefore, the objective of the study is to evaluate the constitutive expression of c-REL in uveal melanoma patients and its prognostic significance.
Detection of c-REL expression was carried out by immunohistochemistry in all 75 patients, and qRT-PCR performed on 58 fresh cases of uveal melanoma along with IL-6 status. Immunoblot was performed to validate immunohistochemistry results. Expression of c-REL protein correlated with clinicopathological parameters and overall survival of patients.
Immunohistochemistry results revealed nuclear expression of the c-REL protein (56%) in our cases. Out of 75 cases, 31 cases showed nuclear expression, and 11 cases had cytoplasmic expression. qRT-PCR showed upregulation of the REL gene in 56.89% cases at the transcriptional level. There was a statistically significant difference in the overall survival of patients with c-REL nuclear immunopositivity (p = 0.0048). On multivariate analysis, scleral invasion and c-REL nuclear expression found to be an independent prognostic factor (p < 0.05)
To the best of our knowledge, this was the first study reporting the expression of the c-REL protein in uveal melanoma. Strong nuclear immunoexpression of c-Rel suggests NFκB pathway activation which might be involved in the progression of the disease. Differential expression of c-REL protein may be used as an attractive target for the development of anticancer strategies.
KeywordsUveal melanoma c-REL Overall survival
Mithalesh Kumar Singh was thankful to Indian Council of Medical Research for providing Senior Research Fellowship (SRF). We are grateful to Mr. Pankaj Kumar for providing technical support in IHC.
MKS and SK are responsible for the conception or design of the work. MKS, LS and KC contribute the acquisition, analysis, or interpretation of data for the work. NP, and RM provide the tissue samples. SB helps in the follow-up of the patients. SS helps in reviewing the histopathology slides. All authors finally approved the manuscript version to be published. SK is the guarantor of the article.
Compliance with ethical standards:
Conflict of interest
The authors declare that they have no conflict of interest.
The study was approved by Institutional Ethical Committee, All India Institute of Medical Sciences, New Delhi, India and conducted in accordance with the ethical standards.
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