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Clinical impact of L1CAM expression measured on the transcriptome level in ovarian cancer.

ABSTRACT: High expression of L1 cell adhesion molecules (L1CAM) has been repeatedly shown to be associated with aggressive disease behavior, which translates in poor clinical outcome in various cancer entities. However, in ovarian cancer results based either on immunohistochemistry or cytosolic protein quantifications remained conflicting regarding clinical behavior. In the present work we assessed L1CAM expression on the transcriptome level with the highly sensitive quantitative real-time PCR (qRT-PCR) to define its relevance in ovarian cancer biology.There was a significant difference in L1CAM high and low mRNA expressing cancers with regard to disease-free (p=0.002) and overall survival (p=0.008). L1CAM proofed to be an independent predictor for disease progression (HR 1.8, p=0.01) and overall survival (HR 1.6, p=0.04). Furthermore, a significant positive correlation between the level of L1CAM and the grade of tumor differentiation (p=0.04), the FIGO stage (p=0.025) as well as the histological subtype (p= 0.002) was found.This study included fresh frozen tissue samples of 138 patients with FIGO I-IV stage ovarian cancer. L1CAM mRNA expression was determined using qRT-PCR. In the calculations special attention was put on the various histological subtypes. In survival analysis median L1CAM mRNA expression obtained in the entire cohort of ovarian cancer samples was used as a cut-off to distinguish between high and low L1CAM mRNA expression.L1CAM mRNA expression appears to play a substantial role in the pathophysiology of ovarian cancer that is translated into poor clinical outcome. Additionally humanized L1CAM antibodies, which can serve as potential future treatment options are under testing.

SUBMITTER: Abdel Azim S

PROVIDER: S-EPMC5095069 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

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Clinical impact of L1CAM expression measured on the transcriptome level in ovarian cancer.

Abdel Azim Samira S Duggan-Peer Michaela M Sprung Susanne S Reimer Daniel D Fiegl Heidi H Soleiman Afschin A Marth Christian C Zeimet Alain G AG

Oncotarget 20160601 24

<h4>Background</h4>High expression of L1 cell adhesion molecules (L1CAM) has been repeatedly shown to be associated with aggressive disease behavior, which translates in poor clinical outcome in various cancer entities. However, in ovarian cancer results based either on immunohistochemistry or cytosolic protein quantifications remained conflicting regarding clinical behavior. In the present work we assessed L1CAM expression on the transcriptome level with the highly sensitive quantitative real-t ...[more]

PMID: 27174921

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Project description:The aim of the present study was to evaluate the expression of the chemokine ligand 18 (CCL18) gene in ovarian cancer and to investigate the effects of its overexpression or suppression on growth, invasion, and metastasis in an ovarian carcinoma cell line (SKOV3) in vitro. CCL18 mRNA expression in epithelial ovarian carcinoma (EOC), benign ovarian tumor and normal ovarian tissues was measured by fluorescence quantitative polymerase chain reaction. A CCL18 restructuring plasmid was constructed, and SKOV3 cells were transfected with the plasmid DNA in vitro. A restructuring interference vector was also transfected into CCL18-positive SKOV3 cells. The growth curves, cell cycle distribution, and invasive, migrative and adhesive capacities of SKOV3 cells following overexpression and suppression of CCL18 were evaluated by MTT assay, flow cytometry, Transwell assay, migration assay, and the fibronectin adhesion method, respectively. The positive expression rate of CCL18 in EOC was significantly higher than in benign ovarian tumor (P = 0.002) and normal ovarian tissues (P = 0.003). However, there was no statistical significance in the expression of CCL18 with regard to clinical pathology (including histological classification, pathological grade and surgical pathological stage), and the median survival times of CCL18-positive and CCL18-negative patients did not differ significantly. The invasive, migrative, and adhesive capacities of SKOV3-CCL18 cells were significantly higher than those of SKOV3 and SKOV3-vector cells (P < 0.05). However, there was no significant difference in cell proliferation between the SKOV3-CCL18 and negative control cells. The invasive, migrative, and adhesive capacities of the pSilencer4.1-CCL18-small interfering RNA127 group were significantly lower than those of non-transfected pSilencer4.1-negative and pSilencer4.1 groups (P < 0.05). In conclusion, the overexpression and silencing of CCL18 affected invasion, adhesion, and migration in EOC cells; thus CCL18 may have potential as a clinical marker for early diagnosis of malignant ovarian tumors, and as a target molecule in the treatment of ovarian cancer.

Dataset Information

Clinical impact of L1CAM expression measured on the transcriptome level in ovarian cancer.

Publications

Clinical impact of L1CAM expression measured on the transcriptome level in ovarian cancer.

Similar Datasets

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