Navid Sobhani, Giandomenico Roviello, Alberto D’Angelo, Raheleh Roudi, Praveen Kumar Neeli and Daniele Generali,
p53 Antibodies as a Diagnostic Marker for Cancer: A Meta-Analysis
Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine,
Department of Health Sciences, University of Florence, Florence, Italy
Department of Biology and Biochemistry, University of Bath, Bath, UK;
Department of Medicine, University of Minnesota Medical School, Minneapolis, USA;
Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Trieste, Italy
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.
After screening the article according to flow chart in Figure 1, 12 studies were selected [10–21]. A total of 2094 patients were included from these studies. The solid cancer patients were treated with adjuvant chemotherapy (such as cyclophosphamide, docetaxel, fluorouracil, epirubicin, methotrexate, and vinorelbine), anti-HER2 (trastuzumab, pertuzumab or lapatinib), endocrine therapy (such as goserelin, and tamoxifen), or combined treatment with Herceptin, chemotherapy, and the nonsteroidal anti-inflammatory drug celecoxib, also 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. The analysis was performed using a randomeffects model (accounting for effect size heterogeneity; I2 = 19%).