Dataset Information

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

ABSTRACT:

Introduction

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.

Methods

Immunohistochemical 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.

Results

RIP140 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.

Discussion

RIP140 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.

SUBMITTER: Vattai A

PROVIDER: S-EPMC5739643 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Publications

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

Vattai Aurelia A Cavailles Vincent V Sixou Sophie S Beyer Susanne S Kuhn Christina C Peryanova Mina M Heidegger Helene H Hermelink Kerstin K Mayr Doris D Mahner Sven S Dannecker Christian C Jeschke Udo U Kost Bernd B

Oncotarget 20171031 62

<h4>Introduction</h4>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.<h4>Methods</h4>Immunohistochemical analyses were carried out to quantify RIP140 and LCoR expression in ...[more]

PMID: 29285256

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Project description:PURPOSE:Ligand-dependent corepressor (LCoR) and receptor-interacting protein 140 (RIP140/NRIP1) play an important role in the regulation of multiple oncogenic signaling pathways and the development of cancer. LCoR and RIP140 form a nuclear complex in breast cancer cells and are of prognostic value in further prostate and cervical cancer. The purpose of this study was to analyze the regulation of these proteins in the development of cervical intraepithelial neoplasia (CIN I-III). METHODS:Immunohistochemical analysis was obtained to quantify RIP140 and LCoR expression in formalin-fixed paraffin embedded tissue sections of cervical intraepithelial neoplasia samples. Tissue (n?=?94) was collected from patients treated in the Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich, Germany, between 2002 and 2014. Correlations of expression levels with clinical outcome were carried out to assess for prognostic relevance in patients with CIN2 progression. Kruskal-Wallis test and Mann-Whitney U test were used for data analysis. RESULTS:Nuclear LCoR overexpression correlates significantly with CIN II progression. Nuclear RIP140 expression significantly increases and nuclear LCoR expression decreases with higher grading of cervical intraepithelial neoplasia. Cytoplasmic RIP140 expression is significantly higher in CIN III than in CIN I or CIN II. CONCLUSION:A decrease of nuclear LCoR expression in line with an increase of dedifferentiation of CIN can be observed. Nuclear LCoR overexpression correlates with CIN II progression indicating a prognostic value of LCoR in cervical intraepithelial neoplasia. Nuclear and cytoplasmic RIP140 expression increases significantly with higher grading of cervical intraepithelial neoplasia underlining its potential role in the development of pre-cancerous lesions. These findings support the relevance of LCoR and RIP140 in the tumorigenesis indicating a possible role of LCoR and RIP140 as targets for novel therapeutic approaches in cervical intraepithelial neoplasia and cervical cancer.

Project description:BackgroundPelvic lymph node metastasis (LNM) is a crucial independent prognostic factor in cervical cancer (CCa) and serves as an indicator for radiation therapy as the primary or an adjuvant treatment option. However, preoperative diagnosis of LNM remains challenging. Thus, we aimed to identify biomarkers of LNM in patients with presumed early-stage CCa.MethodsThe differentially expressed genes (DEGs) between tumours with different lymph node statuses were identified by using The Cancer Genome Atlas database. Then, univariate Cox regression analysis and Kaplan-Meier analyses were utilized to screen overall survival (OS)-associated genes. Multivariate Cox analysis and logistical analysis were utilized to evaluate independent risk factors for OS and LNM, respectively. Subsequently, the protein level of fatty acid binding protein 4 (FABP4) was detected in normal cervical and CCa tissues by immunohistochemistry assays. EdU assays were performed to determine whether FABP4 altered the proliferation of cervical cancer cells. Wound healing and Transwell assays were conducted to explore the effects of FABP4 depletion on migratory and invasive abilities of cervical cancer cells. F-actin fluorescence staining were performed to investigate morphological change and Western blotting analyses were performed to determine epithelial mesenchymal transition-related marker expression and downstream signalling pathways.ResultsA total of 243 DEGs, including 55 upregulated and 188 downregulated DEGs, were found in CCa patients with LNM versus those without LNM. Among these, FABP4 was found to be closely associated with poor OS. Multivariate analysis uncovered that FABP4 was an independent risk factor for OS and LNM in patients with CCa. The immunohistochemical results verified dramatically increased FABP4 expression in CCa tissues compared to normal cervical epithelia and its association with poor OS and LNM. In vitro, The proliferation, migration and invasion of cervical cancer cells were significantly inhibited after knocking down of FABP4, which was accompanied by elevated expression of E-cadherin and downregulated expression of N-cadherin, Vimentin and p-AKT.ConclusionsFABP4 might be a promising biomarker of LNM and survival in patients with early-stage CCa and therefore could significantly contribute to the development of personalized prognosis prediction and therapy optimization.

Dataset Information

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

Introduction

Methods

Results

Discussion

Publications

Investigation of RIP140 and LCoR as independent markers for poor prognosis in cervical cancer.

Similar Datasets

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