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Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts.

ABSTRACT: Objective: Increasing evidence indicates that RAD50, which is involved in the repair process of DNA double-strand break (DSB), is also involved in cancer outcomes. However, its role in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the expression of RAD50 and its prognostic value in HBV-related HCC patients. Methods: 107 and 100 patients with HBV-related HCC from the Affiliated Hospital of Youjiang Medical University of Nationalities (AHYMUN) and the Affiliated Hospital of Nantong University (AHNU), respectively, were enrolled in the study. The distribution of the categorical clinical-pathological data and the levels of RAD50 expression were compared with a ?2 test. Immunohistochemistry (IHC) staining of RAD50 was performed. A partial likelihood test based on univariate and multivariate Cox regression analysis was developed to address the influence of independent factors on disease-free survival (DFS) and overall survival (OS). The Oncomine online database was used to analyse and validate the differential expression of RAD50. The Kaplan-Meier method and a log-rank test were performed to assess the influence of RAD50 on survival at different levels. Results: RAD50 was highly expressed in HCC tissues compared to normal tissues and was significantly correlated with OS in the Cancer Genome Atlas (TCGA) cohort. The validation analysis indicated that significantly increased levels of RAD50 were expressed in HCC tissues in the two independent cohorts. In addition, HCC patients with elevated RAD50 expression levels showed poor OS and DFS in the AHYMUN cohort and decreased OS and DFS in the AHNTU cohort. Conclusion: In conclusion, our study reveals that elevated RAD50 expression is significantly correlated with cancer progression and poor survival in HBV-related HCC patients. These data suggest that RAD50 may act as an oncogene and may serve as a promising target for the therapy of HBV-related HCC patients.

SUBMITTER: Liu W

PROVIDER: S-EPMC7477405 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts.

Liu Wangrui W Xu Wenhao W Chen Yuyan Y Gu Liugen L Sun Xiaolei X Qu Yuanyuan Y Zhang Hailiang H Liu Xiaojuan X Huang Haineng H

Journal of Cancer 20200814 20

<b>Objective:</b> Increasing evidence indicates that RAD50, which is involved in the repair process of DNA double-strand break (DSB), is also involved in cancer outcomes. However, its role in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains unclear. This study was designed to investigate the expression of RAD50 and its prognostic value in HBV-related HCC patients. <b>Methods:</b> 107 and 100 patients with HBV-related HCC from the Affiliated Hospital of Youjiang Medical Univ ...[more]

PMID: 32922536

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Project description:BackgroundDNA double strand break repair is important to preserve the fidelity of our genetic makeup after DNA damage. Rad50 is one of the components in MRN complex important for DNA repair mechanism. Rad50 mutations can lead to microcephaly, mental retardation and growth retardation in human. However, Rad50 mutations in human and other organisms have never been gathered and heuristically compared for their deleterious effects. It is important to assess the conserved region in Rad50 and its homolog to identify vital mutations that can affect functions of the protein.MethodIn this study, Rad50 mutations were retrieved from SNPeffect 4.0 database and literature. Each of the mutations was analyzed using various bioinformatic analyses such as PredictSNP, MutPred, SNPeffect 4.0, I-Mutant and MuPro to identify its impact on molecular mechanism, biological function and protein stability, respectively.ResultsWe identified 103 mostly occurred mutations in the Rad50 protein domains and motifs, which only 42 mutations were classified as most deleterious. These mutations are mainly situated at the specific motifs such as Walker A, Q-loop, Walker B, D-loop and signature motif of the Rad50 protein. Some of these mutations were predicted to negatively affect several important functional sites that play important roles in DNA repair mechanism and cell cycle signaling pathway, highlighting Rad50 crucial role in this process. Interestingly, mutations located at non-conserved regions were predicted to have neutral/non-damaging effects, in contrast with previous experimental studies that showed deleterious effects. This suggests that software used in this study may have limitations in predicting mutations in non-conserved regions, implying further improvement in their algorithm is needed. In conclusion, this study reveals the priority of acid substitution associated with the genetic disorders. This finding highlights the vital roles of certain residues such as K42E, C681A/S, CC684R/S, S1202R, E1232Q and D1238N/A located in Rad50 conserved regions, which can be considered for a more targeted future studies.

Project description:BackgroundLactate dehydrogenase (LDH) is associated with the prognosis of many diseases, but the relationship between LDH and the poor prognosis (recurrence and death) of acute ischemic stroke (AIS) has not been fully clarified. This study aimed to investigate the association between admission LDH level and poor prognosis in patients with AIS.MethodsThis retrospective study enrolled AIS patients treated in Taizhou Hospital of Zhejiang Province from July 2019 to December 2019. Poor prognosis included AIS recurrence and all-cause death at 3, 6, and 18 months. The correction between LDH and poor prognosis or all-cause death was assessed. Lasso Cox expression and multivariate Cox expression analyses were used to evaluate the association of LDH with the risk of poor prognosis and all-cause death, respectively. A nomogram was constructed to evaluate the predictive Values of LDH for the poor prognosis and all-cause death of AIS.Results732 patients were included in the study. Multivariate analysis shows that admission LDH levels were significantly correlated with poor prognosis [odds ratio (OR),1.003; 95% confidence interval (95% CI), 1.001-1.005; P = 0.001] and all-cause death (OR, 1.005; 95% CI, 1.000-1.009; P = 0.031). The correlation analysis showed that admission LDH level was positively correlated with National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score. Time-dependent receiver operating characteristic (td-ROC) curves analysis showed that the AUC values of admission LDH level for predicting prognosis of AIS patients in 3-month, 6-month, 12-month and 18-month were 0.706 (95% CI, 0.604-0.810), 0.653 (95% CI, 0.583-0.723), 0.616 (95% CI, 0.556-60676) and 0.610 (95% CI, 0.552-0.680), respectively. And td-ROC also showed that the AUC values of admission LDH level for predicting all-cause death of AIS patients in 3-month, 6-month,12-month and 18-month were 0.861 (95% CI, 0.764-0.958), 0.824 (95% CI, 0.753-0.890), 0.726 (95% CI, 0.633-0.819) and 0.715 (95% CI, 0.622-0.807), respectively. The nomograms were constructed to create the predictive models of the poor prognosis and all-cause death of AIS.ConclusionHigher LDH levels are independently associated with poor prognosis and all-cause death of AIS.

Dataset Information

Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts.

Publications

Elevated double-strand break repair protein RAD50 predicts poor prognosis in hepatitis B virus-related hepatocellular carcinoma: A study based on Chinese high-risk cohorts.

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