1.Prognostic biomarkers and molecular pathways mediating Helicobacter pylori–induced gastric cancer: a network-biology approach
Farideh KAMAREHEI ; Massoud SAIDIJAM ; Amir TAHERKHANI
Genomics & Informatics 2023;21(1):e8-
Cancer of the stomach is the second most frequent cancer-related death worldwide. The survival rate of patients with gastric cancer (GC) remains fragile. There is a requirement to discover biomarkers for prognosis approaches. Helicobacter pylori in the stomach is closely associated with the progression of GC. We identified the genes associated with poor/favorable prognosis in H. pylori–induced GC. Multivariate statistical analysis was applied on the Gene Expression Omnibus (GEO) dataset GSE54397 to identify differentially expressed miRNAs (DEMs) in gastric tissues with H. pylori–induced cancer compared with the H. pylori–positive with non-cancerous tissue. A protein interaction map (PIM) was built and subjected to DEMs targets. The enriched pathways and biological processes within the PIM were identified based on substantial clusters. Thereafter, the most critical genes in the PIM were illustrated, and their prognostic impact in GC was investigated. Considering p-value less than 0.01 and |Log2 fold change| as >1, five microRNAs demonstrated significant changes among the two groups. Gene functional analysis revealed that the ubiquitination system, neddylation pathway, and ciliary process are primarily involved in H. pylori–induced GC. Survival analysis illustrated that the overexpression of DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, and TXNIP was associated with poor prognosis, while increased MRPS5 expression was related to a favorable prognosis in GC patients. DOCK4, GNAS, CTGF, TGF-b1, ESR1, SELE, TIMP3, SMARCE1, TXNIP, and MRPS5 may be considered prognostic biomarkers for H. pylori–induced GC. However, experimental validation is necessary in the future.
2.Pathogenesis and prognosis of primary oral squamous cell carcinoma based on microRNAs target genes: a systems biology approach
Amir TAHERKHANI ; Shahab Shahmoradi DEHTO ; Shokoofeh JAMSHIDI ; Setareh SHOJAEI
Genomics & Informatics 2022;20(3):e27-
Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, “proteoglycans in cancer” was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.
3.Potential biomarkers and signaling pathways associated with the pathogenesis of primary salivary gland carcinoma: a bioinformatics study
Zeynab BAYAT ; Fatemeh AHMADI-MOTAMAYEL ; Mohadeseh Salimi PARSA ; Amir TAHERKHANI
Genomics & Informatics 2021;19(4):e42-
Salivary gland carcinoma (SGC) is rare cancer, constituting 6% of neoplasms in the head and neck area. The most responsible genes and pathways involved in the pathology of this disorder have not been fully understood. We aimed to identify differentially expressed genes (DEGs), the most critical hub genes, transcription factors, signaling pathways, and biological processes (BPs) associated with the pathogenesis of primary SGC. The mRNA dataset GSE153283 in the Gene Expression Omnibus database was re-analyzed for determining DEGs in cancer tissue of patients with primary SGC compared to the adjacent normal tissue (adjusted p-value < 0.001; |Log2 fold change| > 1). A protein interaction map (PIM) was built, and the main modules within the network were identified and focused on the different pathways and BP analyses. The hub genes of PIM were discovered, and their associated gene regulatory network was built to determine the master regulators involved in the pathogenesis of primary SGC. A total of 137 genes were found to be differentially expressed in primary SGC. The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. TP53, EGF, FN1, NOTCH1, EZH2, COL1A1, SPP1, CDKN2A, WNT5A, PDGFRB, CCNB1, and H2AFX were demonstrated to be the most critical genes linked with the primary SGC. SPIB, FOXM1, and POLR2A significantly regulate all the hub genes. This study illustrated several hub genes and their master regulators that might be appropriate targets for the therapeutic aims of primary SGC.
4.Cinnamic acid derivatives as potential matrix metalloproteinase-9 inhibitors: molecular docking and dynamics simulations
Mohammad Hossein MALEKIPOUR ; Farzaneh SHIRANI ; Shadi MORADI ; Amir TAHERKHANI
Genomics & Informatics 2023;21(1):e9-
Matrix metalloproteinase-9 (MMP-9) is a zinc and calcium-dependent proteolytic enzyme involved in extracellular matrix degradation. Overexpression of MMP-9 has been confirmed in several disorders, including cancers, Alzheimer′s disease, autoimmune diseases, cardiovascular diseases, and dental caries. Therefore, MMP-9 inhibition is recommended as a therapeutic strategy for combating various diseases. Cinnamic acid derivatives have shown therapeutic effects in different cancers, Alzheimer′s disease, cardiovascular diseases, and dental caries. A computational drug discovery approach was performed to evaluate the binding affinity of selected cinnamic acid derivatives to the MMP-9 active site. The stability of docked poses for top-ranked compounds was also examined. Twelve herbal cinnamic acid derivatives were tested for possible MMP-9 inhibition using the AutoDock 4.0 tool. The stability of the docked poses for the most potent MMP-9 inhibitors was assessed by molecular dynamics (MD) in 10 nanosecond simulations. Interactions between the best MMP-9 inhibitors in this study and residues incorporated in the MMP-9 active site were studied before and after MD simulations. Cynarin, chlorogenic acid, and rosmarinic acid revealed a considerable binding affinity to the MMP-9 catalytic domain (ΔGbinding < –10 kcal/ mol). The inhibition constant value for cynarin and chlorogenic acid were calculated at the picomolar scale and assigned as the most potent MMP-9 inhibitor from the cinnamic acid derivatives. The root-mean-square deviations for cynarin and chlorogenic acid were below 2 Å in the 10 ns simulation. Cynarin, chlorogenic acid, and rosmarinic acid might be considered drug candidates for MMP-9 inhibition.
5.Global prevalence of enterobiasis in young children over the past 20 years: a systematic review and metaanalysis
Elham Kia LASHAKI ; Azadeh MIZANI ; Seyed Abdollah HOSSEINI ; Bentolhoda HABIBI ; Khadijeh TAHERKHANI ; Amir JAVADI ; AliReza TAREMIHA ; Samira DODANGEH
Osong Public Health and Research Perspectives 2023;14(6):441-450
Parasitic infections are the most common diseases worldwide, and enterobiasis is a common parasitic infection in children. Various studies have reported on the prevalence of Enterobius vermicularis in different regions of the world. However, no study has gathered and analyzed this data systematically. Our systematic review and meta-analysis investigated the overall prevalence of E. vermicularis among children globally. Data were extracted from 4 available databases for studies published from January 2002 to April 2022. The quality of the included studies was scored based on the standard Strengthening the Reporting of Observational Studies in Epidemiology. A random-effect model was chosen to calculate the pooled prevalence and corresponding 95% confidence interval (CI) according to the degree of heterogeneity in the included studies. Thus, 40 publications (42 data sets) that included 3,279 children with enterobiasis met all criteria and were included in the analysis. The meta-analysis showed that heterogeneity among the included studies was high (Q=4,399.35, I2=99.96%; df=41; p<0.001). The pooled global prevalence of enterobiasis among the studied children was 12.9% (95% CI, 8.2%–17.7%). Our systematic review and meta-analysis estimated that, for the past 20 years, 12.9% of children around the world have been infected with E. vermicularis.