Research Papers
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Item Epigenetic Alterations in Hepatocellular Carcinoma: Mechanisms, Biomarkers, and Therapeutic Implications(Pharmaceuticals, 2025) Wali, Adil Farooq; Ansari, Abid Reza; Mir , Prince Ahad; El-Tanani , Mohamed; Babiker , Rasha; Hussain, Md Sadique; Uppal, Jasreen; Zargar, Asma Ishrat; Mir, Reyaz HassanHepatocellular carcinoma (HCC), the most prevalent primary liver cancer, continues to pose a significant global health burden due to its high mortality rate. In addition to genetic alterations, epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling, and noncoding RNA (ncRNA) dysregulation, play critical roles in HCCinitiation and progression. Notably, miR-375 and miR-483-5p are among the most dysregulated miRNAs in HCC, with their altered expression levels closely associated with tumor stage and patient survival. These epigenetic modifications offer promising therapeu tic avenues due to their reversibility and dynamic nature. Furthermore, specific epigenetic signatures such as CDH1 promoter hypermethylation and HOTAIR overexpression are being explored as potential biomarkers for early detection and treatment response. In this chapter, we review recent advances in the epigenetic landscape of HCC and discuss their diagnostic and therapeutic implications, highlighting their potential to improve patient outcomes through personalized medicine approachesItem Metformin: A Dual-Role Player in Cancer Treatment and Prevention: A Comprehensive Systematic Review and Meta-Analysis(Medicina, 2025) Rangraze, Imran; Wali, Adil Farooq; El-Tanani , Mohamed; Patni , Mohamed Anas; Rabbani, Syed Arman; Babiker, Rasha; Satyam, Shakta Mani; El-Tanani, Yahia; Rizzo, ManfrediBackground and Objectives: Metformin is said to reduce the incidences and deaths resulting from cancer in patients suffering from type 2 diabetes mellitus, but the results have been inconsistent. Perform a systematic review and meta-analysis concentrating on the different outcomes of several cancers while taking into account the impact of metformin use. Materials and Methods: As of 15 October 2024, the literature for Medline, Embase, and WebofScience was systematically searched. ROBINS-I and the RoB 2 tool were used for assessing the risk of bias in observational studies and randomized controlled trials (RCTs), respectively. The strength of the evidence with respect to the GRADE criteria was checked. Random effects meta-analyses were conducted alongside sensitivity analyses, subgroup analyses, and meta-regressions. By utilizing funnel plots as well as Egger’s test and trim-and-fill analysis, publication bias was evaluated. Results: In total, 65 studies were included in the final analyses: Metformin intake was linked to a lower risk of cancer (RR 0.72; 95% CI: 0.64–0.81, I2 = 45%). Significant reductions were observed in breast cancer (RR 0.68; 95% CI: 0.55–0.83) and colorectal cancers (RR 0.62; 95% CI: 0.51–0.76). Evidence certainty fluctuated from moderate to low, though analyses confirmed the results. Plofs funded the publication bias, but adjustment in trim-and-fill did not change the outcome significantly. Conclusions: Metformin intake seems to lower the chances of developing several types of cancers, especially breast and colorectal cancers, but the observational designs hinder determining the causal factors for observational studies. There is a need for large RCTs