Circulating Plasma Epstein-Barr Virus DNA Load During the Follow-up Periods Predicts Recurrence and Metastasis in Nasopharyngeal Carcinoma.

BACKGROUND: Epstein-Barr virus DNA (EBV DNA) load has been identified as a prognostic factor in nasopharyngeal carcinoma (NPC), whereas the dynamic changes in the long period have not been explored. In this study, we evaluated EBV DNA kinetics and its role in the survival. METHODS: We conducted a retrospective review of 900 NPC patients. Plasma EBV DNA levels were measured at various time points after treatment. The correlations of EBV kinetics with recurrence and metastasis were analyzed. After stratifying patients according to the EBV results, survival was compared using Kaplan-Meier estimates. Twelve- and 24-month landmark analyses for overall survival (OS) data were performed according to the EBV groups. RESULTS: Patients with post-EBV of less than 2500 copies/mL achieved better survival than did those with higher ones. Furthermore, patients with continuously elevated EBV DNA expressed significantly poorer OS (hazard ratio [HR], 2.542, 95% confidence interval [CI], 2.077-3.111; P < 0.001), distant metastasis-free survival (HR, 2.970; 95% CI, 2.392-3.687; P < 0.001), locoregional-free survival (HR, 1.699; 95% CI, 1.072-2.692; P = 0.013), and progression-free survival (HR, 2.535; 95% CI, 1.987-3.233; P < 0.001) than did patients with continuously normal EBV or those with elevated levels at any time point. The 5-year OS with elevated EBV was lower than that of the remission group by using the 12- and 24-month landmark analysis. CONCLUSIONS: Elevated EBV DNA after treatment was a better predictive indicator of survival than the baseline concentrations. Furthermore, continuously elevated EBV DNA after treatment indicated recurrence, metastasis, and unfavorable prognosis for NPC. In addition, there were consistent patterns of EBV DNA kinetics during long-term follow-up, which warrant further study.

A combined marker based on plasma D-dimer and serum albumin levels in patients with nasopharyngeal carcinoma is associated with poor survival outcomes in a retrospective cohort study.

Background: Activation of the clotting-fibrinolytic system in cancer patients is common and results in an unfavorable clinical outcome. This study aimed to investigate the role of pretreatment plasma D-dimer levels and the combination of D-dimer and albumin (DA) on the prediction of survival prognosis in patients with nasopharyngeal carcinoma (NPC). Methods: The study comprised 511 patients with NPC. Pretreatment plasma D-dimer and serum albumin levels were measured. DA was classified as a new biomarker where D-dimer and albumin levels were combined and was grouped by the cutoff value of both. The correlations of plasma D-dimer levels with clinicopathological features and survival outcome were calculated using the Chi-square test. Kaplan-Meier estimates were performed to analyze the survival functions and were compared using log-rank tests. Cox proportional hazard regression analysis was used to assess the effects of D-dimer and DA on distant overall survival (OS) and distant metastasis-free survival (DMFS). Results: The median follow-up period was 45.2 months (range 2.1-79.8). Elevated plasma D-dimer levels were positively associated with age at diagnosis (P = 0.034), platelet levels (P = 0.043), and Epstein Barr Virus (EBV) DNA copy number (P = 0.035). Additionally, multivariate analysis demonstrated that elevated plasma D-dimer levels were strongly associated with a poorer OS (HR 2.074, 95% CI 1.190-3.612, P = 0.010), but not DMFS. After adjustment for other variables, DA stratification acted as an independent prognostic marker for OS (P = 0.038) and DMFS (P = 0.031) in patients with NPC, when combined with albumin levels. Conclusions: Increased plasma D-dimer levels accurately predict poor OS and may be an effective independent prognostic factor in patients with NPC. Moreover, in conjunction with serum albumin, DA may serve as a factor in predicting OS and DMFS.

Paraoxonase (PON1) polymorphisms Q192R and L55M are not associated with human longevity: A meta-analysis.

BACKGROUND: Genetic mutations in the paraoxonase 1 (PON1) encoding gene have been considered to affect mortality and of these the functional promoter region polymorphisms Q192R and L55M are among the most widely studied. OBJECTIVE: The aim of this study was to determine whether the Q192R and L55M polymorphisms of PON1 can increase susceptibility to longevity. A meta-analysis was performed to obtain a comprehensive estimation of the association between Q192R and L55M and longevity in long-lived individuals (LLIs) aged 80 years or more. MATERIAL AND METHODS: A search was carried out in the PubMed database (from January 2001 to May 2014) to obtain data on the role of PON1 polymorphisms in longevity and a pooled odds ratio (OR) with a 95% confidence interval (CI) was used to assess the associations. RESULTS: The meta-analysis was based on 9 studies of PON1 Q192R and 5 studies of PON1 L55M that covered a total of 5086 LLIs and 4494 controls. Overall, significantly increased risks were not observed for either Q192R or L55M. The results of the statistical calculations were as follows: R vs. Q (additive model): OR = 1.080, 95% CI = 0.989-1.179, p = 0.088 and RR + RQ vs. QQ (dominant model): OR = 1.099, 95% CI = 0.975-1.240, p = 0.124; M vs. L (additive model): OR = 0.946, 95% CI = 0.862-1.039, p = 0.245 and MM + ML vs. LL (dominant model): OR = 0.951, 95% CI = 0.836-1.081, p = 0.442 for Q192R and L55M, respectively. The results did not change with an age cut-off among the LLIs of ≥ 93 years. CONCLUSION: No evidence that the Q192R and L55M polymorphisms of PON1 impacted on the probability of reaching extreme ages was found although this cannot be completely ruled out; however, the possibility of population-specific effects due to the influence of and interaction between different genes or environmental factors could not be ruled out.

[Synthetic lethal genes to mutant p53].

Targeted therapy has become a powerful approach for cancer treatment. Better understanding of oncogenes as well as synthetic lethal interactions with oncogenes will lead to new strategies for tumor-specific treatment. It is well known that mutant p53 plays an important role in tumorigenesis and tumor development. Thus, understanding the synthetic lethal relationship between p53 mutations and interacting genes in tumor is critical for the personalized treatments of p53 mutant tumors. Synthetic lethal genes to mutant p53 can be divided into cell cycle regulators and non-cell cycle regulators. This paper review show these two types of target genes contribute to synthetic lethal interactions with p53 mutations and potential applications of these interactions in anticancer therapy.