The effect of the TP53 and RB1 mutations on the survival of hepatocellular carcinoma patients with different racial backgrounds

Duan, Xiaohui; Cai, Yi; He, Tingting; Shi, Xiaoliang; Zhao, Juan; Zhang, Hui; Shen, Yao; Zhang, Hongjian; Zhang, Heng; Duan, Wenbin; Jiang, Bo; Mao, Xianhai

doi:10.21037/jgo-21-312

Cited by 5 publications

(4 citation statements)

References 41 publications

(43 reference statements)

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“…Indonesian patients were included in terms of race in the majority of studies. The research revealed similar results on the association of p53 expression with tumor grading, although p53 expression was not associated with HCC stage and subtype, since the results did not reach statistical significance (39). A rigorously defined, easy to use, reproducible and broadly adopted HCC grading system remains to be developed.…”

Section: Discussionmentioning

confidence: 86%

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p53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma

et al. 2023

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The present study aimed to determine the expression levels of p53 in patients with hepatocellular carcinoma (HCC) and to evaluate its association with several HCC-related prognostic factors and in particular, with tumor stage, grade and subtype. Therefore, a cross-sectional study, involving 41 patients with HCC, who underwent surgical resection between January, 2013 and December, 2020 was conducted. To assess the expression levels of p53 in all patients with HCC, immunohistochemical staining was performed. In addition, the association between p53 expression and the clinicopathological characteristics of patients with HCC, including prognostic factors, was evaluated by applying the appropriate statistical analysis methods. The results revealed that among the 41 patients enrolled, 35 patients (85.4%) were positive for p53 expression. A higher percentage of positive p53 expression was observed in male patients >60 years old, with single HCC nodules >5 cm in diameter and vascular invasion, compared with their counterparts. A positive p53 expression was associated with well- and poorly differentiated HCC, but not with tumor stage and subtype. No differences in p53 expression were observed across different tumor stages and subtypes. Additionally, patients with moderately and poorly differentiated HCC exhibited significantly higher p53 expression levels compared with those suffering from well-differentiated HCC. Overall, the results demonstrated that the rate of p53 immuno-positive cells was increased in patients with HCC. In addition, p53 expression was associated with well- and poorly differentiated HCC, thus suggesting its association with a poorer prognosis.

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Section: Discussionmentioning

confidence: 86%

“…In addition, a previous study demonstrated that p53 mutations exhibited discordant effects on the survival of patients with HCC of different racial backgrounds ( 39 ). Therefore, p53 mutations were associated with a worse prognosis in Asian patients compared with Caucasian ones and this effect was associated with their immune cells.…”

Section: Discussionmentioning

confidence: 99%

p53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma

et al. 2023

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“…The unlimited proliferation of HCC cells lacks a termination mechanism, while during LR, cell proliferation can be terminated, and liver mass is precisely regulated. Due to TP53 mutations, the P53 response pathway is frequently deficient in HCC patients [ 24 , 25 ]. Thus, we hypothesized that P53/miR-34a/SIRT1 fails to function during HCC due to the loss or mutation of P53.…”

Section: Resultsmentioning

confidence: 99%

P53/miR-34a/SIRT1 positive feedback loop regulates the termination of liver regeneration

Gong

Cong

et al. 2023

Aging

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Background: The capacity of the liver to restore its architecture and function assures good prognoses of patients who suffer serious hepatic injury, cancer resection, or living donor liver transplantation. Only a few studies have shed light on the mechanisms involved in the termination stage of LR. Here, we attempt to further verify the role of the p53/miR-34a/SIRT1 positive feedback loop in the termination of liver regeneration and its possible relationship with liver cancer. Method: We performed partial hepatectomy (PH) in mice transfected with adenovirus (Ade) overexpressing P53 and adenovirus-associated virus (AAV) overexpressing miR-34a. LR was analyzed by liver weight/body weight, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and cell proliferation, and the related cellular signals were investigated. Bile acid (BA) levels during LR were analyzed by metabolomics of bile acids. Results: We found that the P53/miR-34a/SIRT1 positive feedback loop was activated in the late phase of LR. Overexpression of P53 or miR-34a terminated LR early and enhanced P53/miR-34a/SIRT1 positive feedback loop expression and its proapoptotic effect. T-β-MCA increased gradually during LR and peaked at 7 days after PH. T-β-MCA inhibited cell proliferation and promoted cell apoptosis via facilitating the P53/miR-34a/SIRT1 positive feedback loop during LR by suppressing FXR/SHP. The P53/miR-34a/SIRT1 positive feedback loop was abolished in HCC patients with P53 mutations.

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“…The similarities observed across these studies, despite the different number of overlapping genes, underscores that these high-repair patterns are robust and can be detected with few features. One advantage of our gene list, which covers many DNA repair pathways, was that we included several essential DNA repair genes such as BUB1, BUB1B, RAD51AP1, RB1 , and HORMAD1 that are known to have significant clinical relevance [ 61 , 62 , 63 , 64 , 65 , 66 ] and helped us to define the heterogeneity among the low DNA repair group. The mitotic and replicative factors, along with HR expression, helped to distinguish low-repair groups.…”

Section: Discussionmentioning

confidence: 99%

DNA Damage Repair Classifier Defines Distinct Groups in Hepatocellular Carcinoma

Smith

Alsten

Walens

et al. 2022

Cancers

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DNA repair pathways have been associated with variability in hepatocellular carcinoma (HCC) clinical outcomes, but the mechanism through which DNA repair varies as a function of liver regeneration and other HCC characteristics is poorly understood. We curated a panel of 199 genes representing 15 DNA repair pathways to identify DNA repair expression classes and evaluate their associations with liver features and clinicopathologic variables in The Cancer Genome Atlas (TCGA) HCC study. We identified two groups in HCC, defined by low or high expression across all DNA repair pathways. The low-repair group had lower grade and retained the expression of classical liver markers, whereas the high-repair group had more clinically aggressive features, increased p53 mutant-like gene expression, and high liver regenerative gene expression. These pronounced features overshadowed the variation in the low-repair subset, but when considered separately, the low-repair samples included three subgroups: L1, L2, and L3. L3 had high DNA repair expression with worse progression-free (HR 1.24, 95% CI 0.81–1.91) and overall (HR 1.63, 95% CI 0.98–2.71) survival. High-repair outcomes were also significantly worse compared with the L1 and L2 groups. HCCs vary in DNA repair expression, and a subset of tumors with high regeneration profoundly disrupts liver biology and poor prognosis.

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The effect of the TP53 and RB1 mutations on the survival of hepatocellular carcinoma patients with different racial backgrounds

Cited by 5 publications

References 41 publications

p53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma

p53 expression is associated with tumor stage, grade and subtype in patients with hepatocellular carcinoma

P53/miR-34a/SIRT1 positive feedback loop regulates the termination of liver regeneration

DNA Damage Repair Classifier Defines Distinct Groups in Hepatocellular Carcinoma

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