Alterations of TP53 are associated with a poor outcome for patients with hepatocellular carcinoma: Evidence from a systematic review and meta-analysis

Abstract

Background The prognostic significance of p53 aberration in hepatocellular carcinoma (HCC) remains inconclusive. This review aimed to provide comprehensive evidence on the association of p53 alterations with recurrence-free survival (RFS) and overall survival (OS) in HCC patients. Methods Systematic literature searches were conducted until July 2010. Meta-analysis was performed to estimate prognostic effects of p53 alterations on patient outcomes in HCC. Sensitivity and subgroup analyses were also conducted in the meta-analysis. Results Thirty-seven studies (7 tumour p53 mutation, 23 tumour p53 expression and 7 serum anti-p53 antibodies) were included in the systematic review. The average percentages of p53 mutation, p53 expression upregulation and anti-p53 antibody level elevation in HCC patients were 31.5%, 35.0% and 23.8%, respectively. Tumour p53 alterations were associated significantly with poor patient outcomes in HCC: the summary hazard ratio (HR) of mutant p53 versus wild type p53 phenotype was 2.58 [95% confidence interval (CI): 1.96–3.41] for OS and 3.19 [95% CI: 2.21–4.60] for RFS, respectively; and the summary HR of upregulated p53 expression versus low/undetectable p53 expression was 1.68 [95% CI: 1.49–1.90] for OS and 1.89 [95% CI: 1.34–2.66] for RFS, respectively. However, elevated serum anti-p53 antibody was only associated with poor OS in HCC group with high propotion (≥50%) of hepatitis C virus (HCV) infection [HR: 1.92; 95% CI: 1.30–2.85]. Moreover, sensitivity analyses showed that the results of meta-analyses were not altered. Conclusion HCC patients with p53 mutation and upregulated expression in tumour tissue have a shorter OS and RFS than patients with wild type p53 and low/undetectable p53 expression. However, the prognostic value of serum anti-p53 antibody is required to be further examined.

CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo

“…Many studies have proven that p53 is frequently mutated in human hepatocellular carcinoma (HCC), and the mutations in p53 gene were correlated to tumor stage [10,11]. Systematic review and meta-analysis demonstrated that HCC patients with p53 mutation have a shorter recurrence-free survival and overall survival than patients with wild-type p53 or low/ undetectable p53 expression [12]. All these revealed that p53 mutation played a pivotal role in the pathogenesis of HCC.…”

Crosstalk between EGFR and p53 in Hepatocellular Carcinoma

“…Mutant forms of p53 have a prolonged halflife, which favors intranuclear accumulation, becoming detectable immunohistochemically (Zhou et al, 2006). In several studies, the overexpression of p53 in the serum or liver tissues of HCC patients was associated with a poorer prognosis, a shorter survival time and tumor recurrence (Caruso et al, 1999;Hsia et al, 2000;Qin et al, 2001;Liu et al, 2012). In our research, overexpression of p53 was found in 44% of HCCs.…”

ATXN7 Gene Variants and Expression Predict Post-Operative Clinical Outcomes in Hepatitis B Virus-Related Hepatocellular Carcinoma

“…In addition, Gatchel et al [23] found that insulin-like growth factor (IGF) pathway was involved in SCA7 disease. There have been many studies that reported that both TP53 and IGF play a critical role in the occurrence and prognosis of HCC [24][25][26][27][28]. Recent studies demonstrated that ATXN7 was associated with breast cancer susceptibility and prognosis of RCC [15,16].…”