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.

Results

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%).