Gene-gene interaction network analysis of ovarian cancer using TCGA data

Abstract

BackgroundThe Cancer Genome Atlas (TCGA) Data portal provides a platform for researchers to search, download, and analysis data generated by TCGA. The objective of this study was to explore the molecular mechanism of ovarian cancer pathogenesis.MethodsMicroarray data of ovarian cancer were downloaded from TCGA database, and Limma package in R language was used to identify the differentially expressed genes (DEGs) between ovarian cancer and normal samples, followed by the function and pathway annotations of the DEGs. Next, NetBox software was used to for the gene-gene interaction (GGI) network construction and the corresponding modules identification, and functions of genes in the modules were screened using DAVID.ResultsOur studies identified 332 DEGs, including 146 up-regulated genes which mainly involved in the cell cycle related functions and cell cycle pathway, and 186 down-regulated genes which were enriched in extracellular region par function, and Ether lipid metabolism pathway. GGI network was constructed by 127 DEGs and their significantly interacted 209 genes (LINKERs). In the top 10 nodes ranked by degrees in the network, 5 were LINKERs. Totally, 7 functional modules in the network were selected, and they were enriched in different functions and pathways, such as mitosis process, DNA replication and DNA double-strand synthesis, lipid synthesis processes and metabolic pathways. AR, BRCA1, TFDP1, FOXM1, CDK2, and DBF4 were identified as the transcript factors of the 7 modules.Conclusionour data provides a comprehensive bioinformatics analysis of genes, functions, and pathways which may be involved in the pathogenesis of ovarian cancer.

Genetic and molecular analyses reveal G6PC as a key element connecting glucose metabolism and cell cycle control in ovarian cancer

“…We suppose that G6PC opens a novel perspective for OvCa treatment, namely targeting glycogenolysis. Nonetheless, unlike the TCGA Renal Cell Carcinoma Project, which identifies metabolic shift as a pivotal abnormality in tumour progression [8], the OvCa consortium has not listed metabolic change as an outstanding finding in their report [5] nor have the subsequent TCGA reproducers identified any significant changes in glucose metabolism in OvCa [20][21][22][23][24][25]. In the pilot stage of the current study, we have also screened expression of genes within glycolytic, PPP, glycogenolytic pathways, etc., and we have found that glycogenolysis is not notably increased in OvCa.…”

Role of MTDH, FOXM1 and microRNAs in Drug Resistance in Hepatocellular Carcinoma

“…FOXM1 expression can also be induced by other mechanisms including (i) increased transcription through the action of transcription factors E2F, c-Myc, and hypoxia-inducible factor-1 (HIF-1) [13][14][15]; (ii) loss transcription repression due to mutations in the tumor suppressor p53 (seen in approximately half of HCC patients) [16][17][18] and (iii) decreased expression of microRNAs (miRNAs) such as miR-149 and miR-134 which down-regulate FOXM1 post-transcriptionally [19,20]. Bioinformatic analyses of genome-wide transcriptional sequencing data in HCC have identified alterations of the FOXM1 transcription network including downstream FOXM1 effectors AURKB, BIRC5, CCNB1, CCNB2 and NEK2 [21,22].…”

CYP2E1 and GSTM1 gene polymorphisms, environmental factors, and the susceptibility to lung cancer

“…7 GSTM1 gene polymorphism can change the ability of the enzymes' activation or deactivation of the heterologous substrate, which can affect individual susceptibility to lung cancer after exposure. [8][9][10][11] Previous studies somehow identified the functional role of CYP2E1 or GSTM1 polymorphism and lung cancer risk; several studies also showed the synergistic interaction between gene polymorphisms and environmental cancerogens, 12 and gene-gene interaction among metabolic enzyme genes, 13,14 but interactions between CYP2E1 and GSTM1 polymorphism, these polymorphisms and environmental factors have seldom been reported, 15 and the results of these studies are not consistent. Besides, lung cancer ranks the first both in incidence and mortality rates of cancer in Zhejiang Province in recent years.…”