Abstract
Importance: The protein p53 is an unequivocal tumor suppressor that is altered in half of all cancers. The immune system produces systemic p53 autoantibodies (p53 Abs) in many cancer patients. Objective: This systemic review and meta-analysis focuses on the prognostic value of p53 Abs expressed in the serum of patients with solid tumors. Data Sources: All the clinical investigations were searched on PubMed from the first study dated 1993 until May 2021 (date of submission of the manuscript). Study Selection: Studies were included that met the following criteria: (1) participants with cancer; (2) outcome results expressed in relation to the presence of a p53 antibody; (3) a primary outcome (disease-free survival, overall survival or progression-free survival) expressed as hazard ratio (HR). The following exclusion criteria were used: (1) insufficient data available to evaluate outcomes; (2) animal studies; (3) studies with less than 10 participants. As a result, 12 studies were included in the analysis. Data Extraction and Synthesis: PRISMA guidelines were used for abstracting and assessing data quality and validity by three independent observers. The summary estimates were generated using a fixed-effect model (Mantel–Haenszel method) or a random-effect model (DerSimonian–Laird method), depending on the absence or presence of heterogeneity (I2). Main Outcome(s) and Measure(s): The primary study outcome was to determine the prognostic value of p53 Abs from a large population of patients with solid tumors, as determined before data collection. Results: In total, 12 clinical studies involving 2094 patients were included in the meta-analysis, and it was determined that p53 Abs expression in the serum significantly correlated with poorer survival outcomes of cancer patients (95% CI 1.48 [1.24, 1.77]; p < 0.00001). Conclusions and Relevance: This is the first meta-analysis proving the diagnostic utility of p53-Abs for cancer patients in predicting poorer outcomes. The serum-p53 value (s-p53-value) may be useful for future theranostics.
Highlights
The P53 protein is an unequivocal tumor suppressor mutated in almost half of human cancers [1,2,3,4]
The solid cancer patients were treated with adjuvant chemotherapy, anti-HER2, endocrine therapy, or combined treatment with Herceptin, chemotherapy, and the nonsteroidal anti-inflammatory drug celecoxib, including radiotherapy or a surgical component in some cases (Tables 1 and 2)
The pooled analysis revealed that s-p53-Abs is a negative prognostic factor (HR: 148 [1.24, 1.77]; p < 0.0001, Figure 2) in cancers
Summary
The P53 protein is an unequivocal tumor suppressor mutated in almost half of human cancers [1,2,3,4]. It is autoregulated by MDM2, an E3 ubiquitin ligase [5,6]. The p53 mutation in cancer (p53-mut) does not activate the expression of the E3 ligase. In many cancer patients the p53-wt region is exposed and serum antibodies are generated against p53-wt. These can be detected by ELISA method. The roles of these antibodies are not yet clearly understood
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