A Therapeutic Application of Systematic Review with Meta-analysis: Epigenetic Analysis Tools and Cancer’s Therapy Assessment
Epigenetics will produce a plethora of novel biomarkers to aid in the refinement of cancer therapies and patient drug response; they can be utilised as markers to predict clinical outcome and the likelihood of relapse after chemotherapies.
According to a Prisma flow chart, a total of 1302 articles were retrieved, 151 full-text articles were assessed for eligibility, and 47 studies with low to moderate quality were found to be eligible and involved in systematic review as a qualitative phase, while only 19 studies with moderate quality met the meta-analysis criteria, with a total of 6,086 patients from more than 25 countries.
Only two epigenetic alterations, DNA methylation and histone modifications, were employed to assess the response outcomes of cancer therapy, according to a comprehensive study. DNA methylation was discovered to be the most well-known epigenetic change, which was linked to either better or worse outcomes based on the connected gene, which might be oncogenes or tumour suppressor genes.
The epigenetic DNA methylation has a tendency to predict outcomes (HR= 0.603, CI= 0.462-0.788) in distinct cancer types treated with chemotherapeutic drugs, surgery, and radiotherapy, according to both fixed and random meta-analysis models. However, there were reports of substantial heterogeneity and publication bias. The reasons for heterogeneity were investigated using sub-groups analysis, and they appear to be linked to clinical and methodological variations among the studies.
The first grouping, oncogene methylation or DNA repair gene methylation, exhibited improved cancer patient outcome prediction (HR= 0.5, CI= 0.45-0.55), with minimal publication bias and heterogeneity (Q= 25.24, and I2 = 40.58 percent) among the studies. The second subgroup found that methylation of tumour suppressor genes was linked to poorer outcomes (HR= 2.07, CI= 1.77-2.43), with no heterogeneity (Q= 1.73, and I2 = 0.00) between studies.
Our findings revealed that methylation of the MGMT gene promoter was a strong outcomes predictor (HR=0.528, CI= 0.493-0.566) of cancer patients, particularly when alkylating chemotherapeutic agents were used with or without radiotherapy. Furthermore, the correlation of MGMT with overall survival revealed that methylation of the MGMT promoter was a good predictive biomarker of cancer therapies. These results had minimal heterogeneity (Q= 28.35, and I2= 43.57), and there was no evidence of publication bias.
The three sensitivity analysis techniques for MGMT-promoter methylation as a good predictive biomarker; statistical models, one study removal, and study design revealed that the pooled effect did not differ when the statistical models (fixed or random) of meta-analysis, or one study removal analysis, or study design change were changed.
Regarding the use of epigenetic tools in cancer therapy assessment, large articles with varied designs were dispersed over 13% of the global countries, representing around 6000 patients of low to moderate quality.
Due to clinical and methodological variability among the research, meta-analysis corroborated the systematic review findings regarding DNA-methylation as the best epigenetic tool with substantial heterogeneity and publication bias.
Finally, we conclude that MGMT gene methylation can be used as a predictive biomarker for cancer therapies and is associated with improved overall survival. These findings were not based on a single study and were not affected by changes in statistical models or study designs. Additionally, the unpublished or unretrieved studies in our review had no effect on the findings.
Hind Mohammed Osman Khalifa
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Omdurman Islamic University, P.O. Box 382, Omdurman, Sudan.
Aimun Abdelgaffar Elhassan Ahmed
Department of Pharmacology, Faculty of Pharmacy, P.O. Box 382, Omdurman Islamic University, Omdurman, Sudan and Department of Pharmacology, Faculty of Medicine, Al Baha University, P.O. Box 1988, KSA.