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Review
. 2015 Oct 9;10(10):e0140351.
doi: 10.1371/journal.pone.0140351. eCollection 2015.

Prognostic Role of Serum Antibody Immunity to p53 Oncogenic Protein in Ovarian Cancer: A Systematic Review and a Meta-Analysis

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Free PMC article
Review

Prognostic Role of Serum Antibody Immunity to p53 Oncogenic Protein in Ovarian Cancer: A Systematic Review and a Meta-Analysis

Marica Garziera et al. PLoS One. .
Free PMC article

Abstract

Objective: Serum p53 autoantibodies (p53-AAbs) are the product of an endogenous immune response against p53 overexpression driven by the ovarian tumour. The p53-AAbs are detectable only in a subset of patients. To date, the evidence of an association between the presence of p53-AAbs and ovarian cancer outcomes has been poorly investigated.

Methods: A systematic literature search was performed to identify eligible studies investigating the association of serum p53-AAbs and overall survival (OS) and disease free survival (DFS). Associations between presence of serum p53-AAbs and baseline tumour characteristics were also evaluated. Pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CI) were computed to estimate the prognostic impact of serum p53-AAbs. Heterogeneity between studies was assessed.

Results: A total of 583 patients (7 studies) for OS and 356 patients (4 studies) for DFS were included in the meta-analysis. Presence of p53-AAbs was not associated to OS (pooled uni- multivariate HR = 1.09; 95% CI: 0.55-2.16), and a large heterogeneity was found. When only multivariate HRs were pooled together (4 studies), presence of p53-AAbs was significantly associated to a better OS (pooled HR = 0.57; 95% CI: 0.40-0.81), and no significant heterogeneity was observed. A reduced DFS was associated to p53-AAbs (pooled uni- multivariate HR = 1.37; 95% CI: 0.83-2.25), though not significantly and with a moderate heterogeneity.

Conclusions: The prognostic significance of serum p53-AAbs in ovarian cancer was diverging according to uni or multivariate models used. Since the results of this work were based on only few investigations, large prospective studies are needed to better define the role of antibody immunity against p53.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA Flow chart describing the search for relevant studies used in this meta-analysis.
Fig 2
Fig 2. Forest plots of adjusted Hazard Ratios (HRs) for Overall Survival in ovarian cancer according to presence of p53-AAbs.
Random effect models were computed. (A) Pooled analysis considering uni- multivariate HRs (7 studies); (B) pooled analysis with only multivariate HRs (4 studies).
Fig 3
Fig 3. Forest plot of adjusted Hazard Ratios (HRs) for presence of p53-AAbs and Disease Free Survival in ovarian cancer according to p53-AAbs status.
Fig 4
Fig 4. Publication bias assessment of the studies assessing p53-AAbs presence and OS in ovarian cancer.
(A) Funnel plot for publication bias assessment of pooled OS; (B) Egger’s linear regression test.
Fig 5
Fig 5. Sensitivity analysis.
The analysis was conducted by estimating the average HR in the absence of each study. (A) Sensitivity analysis of all studies assessing associations between presence of p53-AAbs in ovarian cancer for OS, and DFS (B).

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Grant support

This work was supported by grant «Application of advanced nanotechnology in the development of innovative cancer diagnostic tools», AIRCx1000 Special Program Molecular Oncology (Grant number 12214). The funder has no role in the study design, data collection and analysis, or manuscript preparation.
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