I Gde Sastra Winata

Bioinformatics Analysis Reveals Distinct Oncogenic Profiles of HPV-16 and HPT-18 to Other Subtypes in Cervical Cancer

HPV types 16 and 18 are associated with 70% of invasive cervical cancers. Between these two types of HPV, HPV type 16 is more commonly found in cervical cancer patients, whereas HPV type 18 is less frequently reported. Currently, the molecular mechanism underlying the increased cancer risk in HPV type 16, compared to HPV type 18, has not yet been fully elucidated. This paper aims to identify the factors that make HPV type 16 the primary contributor to cervical cancer by comparing gene expression profiles with those of HPV type 18. The examination began after obtaining the RNA sequencing dataset (GSE192897). The dataset's genes were then analyzed to identify differentially expressed genes (DEGs) using the GEO2R tool. With the help of Enrichr and SRplot tools, the DEGs were first enriched and analyzed through Gene Ontology (GO), GeDiPNet, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, a protein-protein interaction (PPI) network was constructed using Cytoscape, and the top ten hub genes were ranked with the help of CytoHubba. DEG analysis revealed 128 differentially expressed genes (DEGs), including 14 upregulated and 114 downregulated genes. The upregulated genes were associated with positive regulation of interferon-beta production, vesicle-related processes, endopeptidase inhibitor activity, and interferon-gamma signaling. The downregulated genes were linked to positive regulation of cell motility, the endoplasmic reticulum lumen, cytokine activity, and signal transduction. There are several differentially expressed genes (DEGs) in HPV type 16 compared to type 18; these upregulated genes may potentially play a role in promoting cervical cancer development more significantly than HPV type 18. These DEGs underscore the urgency of implementing HPV genotyping tests to identify HPV types with higher cervical cancer prevalence. This analysis identified BUB1, DLGAP5, and ASPM as key genes specifically expressed in HPV-16/18-related cervical cancer, suggesting their potential as biomarkers for prognosis and disease progression.

Tumor Budding Significance as a Biomarker for Clinicopathology and Prognostic Evaluation in Gynecological Malignancy: A Bayesian Meta-Analysis

Tumor budding (TB) has been recommended as a marker for prognosis and therapeutic decision-making in various types of cancer, yet it has not been comprehensively studied in gynecological malignancies. This study aimed to evaluate the relationship between TB and clinicopathological features, as well as prognosis, in patients with gynecological malignancies, using a Bayesian meta-analysis design. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 protocol was followed. A systematic literature search was conducted using PubMed, ScienceDirect, and Cochrane databases. A meta-analysis was performed to assess the relationship between TB and clinicopathological parameters using odds ratios (ORs). Prognostic outcomes were analyzed using hazard ratios (HRs). Specific Bayesian priors were applied to each variable. Data analysis was conducted using R (version 4.4.0). Eighteen cohort studies (n = 3,320) involving patients with cervical and endometrial cancer were included. Bayesian meta-analysis showed that TB was significantly associated with clinicopathological parameters, specifically cancer stage (OR=2.91; 95%CrI: 1.86-4.41; prediction interval (PI) OR=2.92; 95%CrI: 0.82-9.92; τ2=0.53), grading (OR=5.00; 95%CrI: 2.83-8.76; PI OR=5.00; 95% CrI: 0.89-27.87; τ2=0.77), nodal involvement (OR=3.63; 95%CrI: 2.41-5.47; PI OR=3.63; 95%CrI: 0.85-15.52; τ2=0.66), and lymphovascular invasion (LVI) (OR=4.22; 95%CrI: 2.52-6.92; PI OR=4.22; 95%CrI: 0.63-27.80; τ2=0.89). Overall survival (OS) showed an HR of 2.14 (95%CrI: 1.27-3.63; PI HR=2.14; 95%CrI: 0.83-5.58; τ2=0.25) and DFS showed an HR of 1.20 (95%CrI: 0.77-1.59; PI HR=1.21; 95%CrI: 0.14-2.20; τ2=0.42). Tumor budding is significantly associated with clinicopathological features and prognosis in patients with gynecological malignancies.