Abstract
IntroductionRIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers. The aim of the study was to analyze the expression of RIP140 and its partner LCoR in cervical cancers, to decipher their relationship with histone protein modifications and to identify a potential link with patient survival.MethodsImmunohistochemical analyses were carried out to quantify RIP140 and LCoR expression in formalin-fixed paraffin-embedded tissue sections cervical cancer samples. Correlations of RIP140 and LCoR expression with histopathological variables were determined by correlation analyses. Survival rates of patients expressing low or high levels of RIP140 and LCoR were compared by Kaplan-Meier curves.ResultsRIP140 overexpression was associated with a significantly shorter overall survival of cervical cancer patients. This effect was significant in the squamous cell carcinoma subtype but not in adenocarcinomas. RIP140 is no longer a significant negative prognosticator for cervical cancer when LCoR expression is low.DiscussionRIP140 is an independent predictor of poor survival of patients with cervical cancer. Patients with tumors expressing low levels of both RIP140 and LCoR showed a better survival compared to patients expressing high levels of RIP140. Modulation of RIP140 and LCoR may represent a novel targeting strategy for cervical cancer prevention and therapy.
Highlights
RIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers
Patients with tumors expressing low levels of both RIP140 and ligand dependent corepressor (LCoR) showed a better survival compared to patients expressing high levels of RIP140
A total of 172 (71.7%) of the cervical cancer tissue samples showed positive RIP140 staining in the nucleus with a median immunoreactive score (IRS) of 3 while 68 (28.3 %) did not express nuclear RIP140 (IRS=0 or 1). 10 cases could not be assessed for technical reasons
Summary
RIP140 (Receptor Interacting Protein) is involved in the regulation of oncogenic signaling pathways and in the development of breast and colon cancers. The aim of the study was to analyze the expression of RIP140 and its partner LCoR in cervical cancers, to decipher their relationship with histone protein modifications and to identify a potential link with patient survival. A persistent infection with high-risk human papillomavirus (HR-HPV) is the major leading cause of cervical cancer [3]. When HPV replicates, the viral E6 oncoprotein is expressed and disturbs the cell cycle [4]. The epigenetic regulation in cervical cancers can be modified through altered mechanisms such as DNA methylation and post-translational modifications of histone www.impactjournals.com/oncotarget proteins [7]. We showed that histone H3 acetyl K9 (H3K9ac) and histone H3 trimethyl K4 (H3K4me3) were independent markers for poor prognosis and short overall survival (OS) in cervical cancer patients [8]
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