The relationship between RASSF1A gene promoter methylation and the susceptibility and prognosis of melanoma: A meta-analysis and bioinformatics

Abstract

BackgroundThe function of the tumor suppressor gene RASSF1A in cancer cells has been detailed in many studies. However, due to the methylation of its promoter, the expression of RASSF1A is missing in most cancers. In the literature, we found that the conclusion regarding the relationship between RASSF1A gene promoter methylation and the susceptibility and prognosis of melanoma was not unified. This study adopts the use of a meta-analysis and bioinformatics to explore the relationship between RASSF1A gene promoter methylation and the susceptibility and prognosis of melanoma.MethodsData on melanoma susceptibility were downloaded from the PubMed, Cochrane Library, Web of Science and Google Scholar databases, which were analyzed via a meta-analysis. The effect sizes were estimated by measuring an odds ratio (OR) with a 95% confidence interval (CI). We also used a chi-squared-based Q test to examine the between-study heterogeneity, and used funnel plots to evaluate publication bias. The data on melanoma prognosis, which were analyzed by bioinformatics methods, were downloaded from The Cancer Genome Atlas (TCGA) project. The effect sizes were estimated by measuring the hazard ratios (HRs) with a 95% confidence interval (CI).ResultsOur meta-analysis included 10 articles. We found that RASSF1A gene promoter methylation was closely related to melanoma susceptibility (OR = 12.67, 95% CI: 6.16 ∼ 26.05, z = 6.90, P<0.0001 according to a fixed effects model and OR = 9.25, 95% CI: 4.37 ∼ 19.54, z = 5.82, P<0.0001 according to a random effects model). The results of the meta-analysis did not reveal any heterogeneity (tau2 = 0.00; H = 1 [1; 1.55]; I2 = 0% [0%; 58.6%], P = 0.5158) or publication bias (t = 0.87, P = 0.4073 by Egger’s test; Z = 0.45, P = 0.6547 by Begg’s test); therefore, we believe that the results of our meta-analysis were more reliable. To explore the relationship between RASSF1A gene methylation, the prognosis of melanoma and the clinical features of this cancer type, we used the melanoma DNA methylation data and clinical data from TCGA project. We found that RASSF1A gene promoter methylation and melanoma prognosis did not demonstrate any relationship (HR was 0.94 (95% CI = [0.69; 1.27], P = 0.694) with disease-free survival and 0.74 (95% CI = [0.53; 1.05], P = 0.106) for overall survival), and no significant difference was observed between RASSF1A gene promoter methylation and the clinical-pathological features of melanoma.ConclusionsIn conclusion, the meta-analysis of the data in these articles provides strong evidence that the methylation status of the RASSF1A gene promoter was strongly related to melanoma susceptibility. Our bioinformatics analysis revealed no significant difference between RASSF1A gene promoter methylation and the prognosis and clinical-pathological features of melanoma.

Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma

“…Conversely, our data did not demonstrate any correlation of RASSF1 with survival. In this regard, previous reports have identified RASSF1 as an independent prognostic factor; however, in a recent meta‐analysis no significant association with survival was found . Although Kaplan–Meier and univariate Cox regression analyses indicated that methylation correlated with poor prognosis, in our cohort only Breslow index and ulceration were independent predictors of patient survival.…”

“…In this regard, previous reports have identified RASSF1 as an independent prognostic factor; 13 however, in a recent meta-analysis no significant association with survival was found. 28 Although Kaplan-Meier and univariate Cox regression analyses indicated that methylation correlated with poor prognosis, in our cohort only Breslow index and ulceration were independent predictors of patient survival. Both histopathological features are wellknown prognostic factors; therefore, methylation events may have clinical utility providing additional prognostic information to these conventional parameters in routine practice.…”

Association Between RASSF1A Promoter Methylation and Testicular Germ Cell Tumor: A Meta-analysis and a Cohort Study

“…Several meta-analysis studies showed an association between RASSF1A promoter hypermethylation and different types of tumors as well as biomarker value of the RASSF1A methylation status (47)(48)(49). This study represents the first meta-analysis of published studies to evaluate the association of RASSF1A promoter hypermethylation with testicular cancer.…”

Association between methylation of RASSF1A and breast cancer: a meta-analysis

“…A number of meta-analysis studies have shown that there is a correlation between hyper-methylation of RASSF1A promoter and different types of tumors, as well as the value of biomarkers for the methylation status of RASSF1A [21][22][23][24][25] . In addition, an important implication from our findings is that hyper-methylation of the promoter of tumor suppressor loci in normal breast tissue may be a precursor to local recurrence.…”