Dataset Information

Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers.

ABSTRACT: High-grade serous ovarian carcinoma (HGSOC) is characterised by alterations in the p53 pathway. The expression levels of p53 isoforms have been shown to be associated with patient survival in several cancers. This study examined the predictive and prognostic effects of the expression levels of TP53 pre-mRNA splicing isoforms and TP53 mutations in tumour tissues in 40 chemotherapy responders and 29 non-responders with HGSOC. The mRNA expression levels from total p53, and total ?133p53, p53?, p53? isoforms were determined by RT-qPCR, and TP53 mutation status by targeted massive parallel sequencing. The results from these analyses were correlated with the clinical outcome parameters. No differential expression of p53 isoforms could be detected between the chemosensitive and chemoresistant subgroups. In a multivariate Cox regression model, high levels of total ?133p53 were found to be an independent prognosticator for improved overall survival (HR?=?0.422, p?=?0.018, 95% CI: 0.207-0.861) and reached borderline significance for progression-free survival (HR?=?0.569, p?=?0.061, 95% CI: 0.315-1.027). TP53 mutations resulting in loss of function or located at known hotspots were predictive of tumour characteristics and disease progression. These findings suggest that total ?133p53 mRNA can be a biomarker for survival in HGSOC.

SUBMITTER: Bischof K

PROVIDER: S-EPMC6437169 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers.

Bischof Katharina K Knappskog Stian S Hjelle Sigrun M SM Stefansson Ingunn I Woie Kathrine K Salvesen Helga B HB Gjertsen Bjorn T BT Bjorge Line L

Scientific reports 20190327 1

High-grade serous ovarian carcinoma (HGSOC) is characterised by alterations in the p53 pathway. The expression levels of p53 isoforms have been shown to be associated with patient survival in several cancers. This study examined the predictive and prognostic effects of the expression levels of TP53 pre-mRNA splicing isoforms and TP53 mutations in tumour tissues in 40 chemotherapy responders and 29 non-responders with HGSOC. The mRNA expression levels from total p53, and total Δ133p53, p53β, p53γ ...[more]

PMID: 30918304

Similar Datasets

Project description:Expression of the progesterone receptor (PR) has been reported to influence survival outcomes in patients with ovarian high-grade serous carcinoma (HGSC). In the present study, we attempted to investigate the association among PR and its isoforms' expression, platinum sensitivity, and survival in ovarian HGSC. This retrospective study reviewed ovarian HGSC patients who received surgery followed by adjuvant chemotherapy. We analyzed total PR and PR isoform-B (PR-B) expression by immunohistochemical staining and quantified using the H-score. Then, we compared platinum sensitivity and survival outcomes between those patients with weak and strong PR-B expression. Cisplatin viability assays were carried out in ovarian HGSC cell lines (OC-3-VGH and OVCAR-3) with different PR-B expression. Among 90 patients, 49 and 41 patients were considered to have platinum-sensitive and platinum-resistant disease, respectively. Pearson's correlation model showed that the H-score of total PR correlated positively with PR-B (r = 0.813). The PR-B H-score of tumors was significantly higher in the platinum-sensitive group (p = 0.004). Multivariate analysis revealed that the PR-B H-score and optimal debulking status were independent factors predicting platinum sensitivity. When compared with strong PR-B expression, patients with weak PR-B had significantly poorer progression-free (p = 0.021) and cancer-specific survival (p = 0.046). In a cell model, cisplatin-resistant OC-3-VGH cells expressed a lower level of PR-B than wild-type cells. Overexpression of PR-B or progesterone could increase cisplatin sensitivity in both OC-3-VGH and OVCAR-3 cells via the mechanism of promoting cisplatin-related apoptosis. When compared to weak PR-B, ovarian HGSC patients with a strong PR-B expression had a better chance of platinum sensitivity and survival, and this finding was compatible with our experimental results. Progesterone seemed to be a platinum sensitizer, but the value of adding progesterone in the treatment of ovarian HGSC should be further investigated.

Dataset Information

Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers.

Publications

Influence of p53 Isoform Expression on Survival in High-Grade Serous Ovarian Cancers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets