arXiv subjects

Sedigheh Behrouzifar

Publications and source records attributed to Sedigheh Behrouzifar.

3 recordsLinked to original sources

arXiv2023

Comparative study of under-expressed prognostic biomarkers and pivotal signaling pathways in colon cancer and ulcerative colitis using integrated bioinformatics approach

Colon cancer is a prevalent gastrointestinal malignancy arising in the colon. Ulcerative colitis(UC) is one of the risk factors of colorectal cancer. The detection of under-expressed biomarkers and molecular mechanisms in UC and colon cancer can lead to effective management of colitis-associated cancer. A total of two mRNA expression datasets (GSE87473 and GSE44076) were downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was used to screen differentially expressed genes (DEGs) between extensive ulcerative colitis samples and healthy samples, limited ulcerative colitis samples and healthy samples, and colon cancer samples and healthy samples. In extensive ulcerative colitis, limited ulcerative colitis and colon cancer groups, 95,69 and 635 under-expressed genes with adjusted p-value<0.05 and log(2) fold change<-2 were detected respectively. Using Cytoscape software, the genes with degree> 15 including CLCA1, SLC26A3, SI, KIT, HPGDS, NR1H4, ADIPOQ, PPARGC1A, GCG, MS4A12, GUCA2A and FABP1 were screened as hub under-expressed genes in colon cancer. In extensive ulcerative colitis, the genes with degree>5 including ABCB1, ABCG2, UGT1A6, CYP2B6 and AQP8 were identified as hub genes. Moreover, the genes including NR1H4, CYP2B6, ABCB1, ABCG2, UGT2A3 and PLA2G12B were detected as hub genes with degree>5 in limited ulcerative colitis. According to inclusion criteria and venn diagram, the downregulated gene NR1H4 was common gene in limited ulcerative colitis and colon cancer. The current in silico study showed that downregulation of CLCA1, PPARGC1A and AQP8 genes may increase cancer cell invasion and metastasis ability.

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arXiv2023

Identifying downregulated hub genes and key pathways in HBV-related hepatocellular carcinoma using systems biology approach

Chronic Hepatitis B (CHB) is an independent risk factor for hepatocellular carcinoma (HCC) initiation without cirrhosis occurrence. Apart from the favorable effects of some antiviral drugs following tumor resection on the survival of HCC patients, the use of these agents is essential lifelong. Thus, designing the target-oriented therapeutic strategies to increase life expectancy in HCC patients would be very important. The present study aimed to identify downregulated hub genes and enriched pathways in HB-related HCC using a systems biology-based approach. Microarray data of GSE121248 were downloaded from gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) with the cut-off criteria of adjusted p < 0.05 and Log Fold-change (FC) < -1.5 were selected. Then, the genes with the highest centrality were detected. Finally, the prognostic values of the hub genes were assessed. Six under-expressed hub genes with the highest interaction degree, Betweenness and Eigenvector centrality were including IGF-1, PTGS2, PLG, HGF, ESR-1 and CYP2B6. Among genes with high centrality, several genes including CYP2C9, ESR-1, CXCL2, CYP2C8, IGF-1, CYP3A4, CYP2E1, CERPINE-1 and PXR were prognostic in HCC. The important repressed pathways were including metabolic pathways and PI3K-Akt and chemokine signaling pathways. The under-expression of several genes implicated in metabolism, differentiation and chemotaxis might be a hallmark of the progression of HCC that can be considered as diagnostic and therapeutic targets.

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arXiv2023

Exploring novel prognostic biomarkers and biologic processes involved in NASH, cirrhosis and HCC based on survival analysis using systems biology approach

There is an unmet need to develop medications or drug combinations which can stop advancement of NASH to liver cirrhosis and HCC. Therefore, identifying key biomarkers based on overall survival and the exploring biological processes involved in the pathogenesis and progression of NASH toward cirrhosis and HCC to improve therapeutic interventions is necessary. The microarray dataset from the GPL13667 platform was downloaded from the Gene Expression Omnibus (GEO). The inclusion criteria for the DEGs included an adjusted p-value <0.05 and a log(2) fold change >1. In the first step, protein-protein interaction (PPI) network of differentially expressed genes (DEGs) in every three groups (NASH, Cirrhosis and HCC) was constructed using STRING online database. In the second step, the DEGs of each group were imported to Cytoscape software separately, and the genes with Degree >3 were selected. In the third step, the genes with Degree >3 were imported to Gephi software (0.9.2 version) and the genes with betweenness centrality >0 were selected. Venn diagram of these genes was depicted for the NASH, cirrhotic and HCC groups. According to venn diagram, 96 (NASH), 30 (cirrhotic) and 213 (HCC) genes were specifically upregulated (based on inclusion criteria). Among specific genes, 22 (NASH), 5 (cirrhotic) and 82 (HCC) genes were with poor overall survival. The overlap among the 3 groups (NASH, Cirrhosis and HCC) contained 4 upregulated genes HLA-F, HLA-DPA1, TPM1 and YWHAZ. From 4 upregulated genes, only YWHAZ gene was with poor overall survival. The present study detected new candidate genes and key biological processes in NASH, cirrhosis and HCC based on overall survival and using in silico analysis. Therefore, performing in vitro and in vivo researches to verify the results is necessary.

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