Bioinformatics analysis has been playing a vital role in identifying potential genomic biomarkers more accurately from an enormous number of candidates by reducing time and cost compared to the wet-lab-based experimental procedures for disease diagnosis, prognosis, and therapies. Cervical cancer (CC) is one of the most malignant diseases seen in women worldwide. This study aimed at identifying potential key genes (KGs), highlighting their functions, signaling pathways, and candidate drugs for CC diagnosis and targeting therapies. Four publicly available microarray datasets of CC were analyzed for identifying differentially expressed genes (DEGs) by the LIMMA approach through GEO2R online tool. We identified 116 common DEGs (cDEGs) that were utilized to identify seven KGs (AURKA, BRCA1, CCNB1, CDK1, MCM2, NCAPG2, and TOP2A) by the protein–protein interaction (PPI) network analysis. The GO functional and KEGG pathway enrichment analyses of KGs revealed some important functions and signaling pathways that were significantly associated with CC infections. The interaction network analysis identified four TFs proteins and two miRNAs as the key transcriptional and post-transcriptional regulators of KGs. Considering seven KGs-based proteins, four key TFs proteins, and already published top-ranked seven KGs-based proteins (where five KGs were common with our proposed seven KGs) as drug target receptors, we performed their docking analysis with the 80 meta-drug agents that were already published by different reputed journals as CC drugs. We found Paclitaxel, Vinorelbine, Vincristine, Docetaxel, Everolimus, Temsirolimus, and Cabazitaxel as the top-ranked seven candidate drugs. Finally, we investigated the binding stability of the top-ranked three drugs (Paclitaxel, Vincristine, Vinorelbine) by using 100 ns MD-based MM-PBSA simulations with the three top-ranked proposed receptors (AURKA, CDK1, TOP2A) and observed their stable performance. Therefore, the proposed drugs might play a vital role in the treatment against CC.

Cervical cancer (CC) is considered as the fourth most common women cancer globally.that shows malignant features of local infiltration and invasion into adjacent organs and tissues. There are several individual studies in the literature that explored CC-causing hub-genes (HubGs), however, we observed that their results are not so consistent. Therefore, the main objective of this study was to explore hub of the HubGs (hHubGs) that might be more representative CC-causing HubGs compare to the single study based HubGs. We reviewed 52 published articles and found 255 HubGs/studied-genes in total. Among them, we selected 10 HubGs (CDK1, CDK2, CHEK1, MKI67, TOP2A, BRCA1, PLK1, CCNA2, CCNB1, TYMS) as the hHubGs by the protein–protein interaction (PPI) network analysis. Then, we validated their differential expression patterns between CC and control samples through the GPEA database. The enrichment analysis of HubGs revealed some crucial CC-causing biological processes (BPs), molecular functions (MFs) and cellular components (CCs) by involving hHubGs. The gene regulatory network (GRN) analysis identified four TFs proteins and three miRNAs as the key transcriptional and post-transcriptional regulators of hHubGs. Then, we identified hHubGs-guided top-ranked FDA-approved 10 candidate drugs and validated them against the state-of-the-arts independent receptors by molecular docking analysis. Finally, we investigated the binding stability of the top-ranked three candidate drugs (Docetaxel, Temsirolimus, Paclitaxel) by using 100 ns MD-based MM-PBSA simulations and observed their stable performance. Therefore the finding of this study might be the useful resources for CC diagnosis and therapies.

Numerous studies conducted globally have explored the possible connection between the IL6 gene variant rs1800795 (G>C) and the risk of several diseases. Nonetheless, the correlation specifically within the Asian population remains inconclusive. Hence, this extensive meta-analysis aims to establish a conclusive correlation between the rs1800795 variant and susceptibility to various diseases among Asians. Fifty eligible articles were chosen from Google Scholar, PubMed, Web of Science, and PMC based on specific inclusion criteria. Odds ratios alongside 95% confidence intervals (CI) were utilized. Additionally, subgroup analysis, publication bias, and sensitivity evaluation were conducted. The analysis, of 14,737 cases and 15,417 controls, showed a notable correlation between the rs1800795 (G>C) single-nucleotide polymorphism and the overall disease susceptibility to all models (p-value <2.5E-05). The ethnicity-specific stratified findings indicated that the C-allele of (C vs. G) model of −174G/C polymorphism expressively elevated the overall disease susceptibility in both East and South Asian populations. The disease-based stratified analyses suggested that the C variant of rs1800795 was related to coronary artery diseases and bronchial asthma (under all models), type 2 diabetes (CG vs. GG), acute pancreatitis (AP) (C vs. G; and CC vs. GG), rheumatoid arthritis (CC+CG vs. GG; CC vs. CG+GG; and C vs. G), and AP (C or CC vs. G or GG respectively). IL6 rs1800795 polymorphism is a highly significant disease risk factor in Asians and can potentially serve as a prognostic biomarker for future disease screening and evaluation. Received: 3 November 2023 | Revised: 18 December 2023 | Accepted: 31 December 2023 Conflicts of Interest The authors declare that they have no conflicts of interest to this work. Data Availability Statement The data that support this work are available upon reasonable request to the corresponding author.

Background and Objectives: Breast cancer (BC) is one of the major causes of cancer-related death in women globally. Proper identification of BC-causing hub genes (HubGs) for prognosis, diagnosis, and therapies at an earlier stage may reduce such death rates. However, most of the previous studies detected HubGs through non-robust statistical approaches that are sensitive to outlying observations. Therefore, the main objectives of this study were to explore BC-causing potential HubGs from robustness viewpoints, highlighting their early prognostic, diagnostic, and therapeutic performance. Materials and Methods: Integrated robust statistics and bioinformatics methods and databases were used to obtain the required results. Results: We robustly identified 46 common differentially expressed genes (cDEGs) between BC and control samples from three microarrays (GSE26910, GSE42568, and GSE65194) and one scRNA-seq (GSE235168) dataset. Then, we identified eight cDEGs (COL11A1, COL10A1, CD36, ACACB, CD24, PLK1, UBE2C, and PDK4) as the BC-causing HubGs by the protein-protein interaction (PPI) network analysis of cDEGs. The performance of BC and survival probability prediction models with the expressions of HubGs from two independent datasets (GSE45827 and GSE54002) and the TCGA (The Cancer Genome Atlas) database showed that our proposed HubGs might be considered as diagnostic and prognostic biomarkers, where two genes, COL11A1 and CD24, exhibit better performance. The expression analysis of HubGs by Box plots with the TCGA database in different stages of BC progression indicated their early diagnosis and prognosis ability. The HubGs set enrichment analysis with GO (Gene ontology) terms and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways disclosed some BC-causing biological processes, molecular functions, and pathways. Finally, we suggested the top-ranked six drug molecules (Suramin, Rifaximin, Telmisartan, Tukysa Tucatinib, Lynparza Olaparib, and TG.02) for the treatment of BC by molecular docking analysis with the proposed HubGs-mediated receptors. Molecular docking analysis results also showed that these drug molecules may inhibit cancer-related post-translational modification (PTM) sites (Succinylation, phosphorylation, and ubiquitination) of hub proteins. Conclusions: This study’s findings might be valuable resources for diagnosis, prognosis, and therapies at an earlier stage of BC.