GENETIC_ASSOCIATION_DB_DISEASE_CLASS analysis of 82 genes in TF-gene regulatory network.

<p>GENETIC_ASSOCIATION_DB_DISEASE_CLASS analysis of 82 genes in TF-gene regulatory network.</p

Altered Expression of Hypoxia-Inducible Factor-1α (HIF-1α) and Its Regulatory Genes in Gastric Cancer Tissues

<div><p>Tissue hypoxia induces reprogramming of cell metabolism and may result in normal cell transformation and cancer progression. Hypoxia-inducible factor 1-alpha (HIF-1α), the key transcription factor, plays an important role in gastric cancer development and progression. This study aimed to investigate the underlying regulatory signaling pathway in gastric cancer using gastric cancer tissue specimens. The integration of gene expression profile and transcriptional regulatory element database (TRED) was pursued to identify HIF-1α ↔ NFκB1 → BRCA1 → STAT3 ← STAT1 gene pathways and their regulated genes. The data showed that there were 82 differentially expressed genes that could be regulated by these five transcription factors in gastric cancer tissues and these genes formed 95 regulation modes, among which seven genes (MMP1, TIMP1, TLR2, FCGR3A, IRF1, FAS, and TFF3) were hub molecules that are regulated at least by two of these five transcription factors simultaneously and were associated with hypoxia, inflammation, and immune disorder. Real-Time PCR and western blot showed increasing of HIF-1α in mRNA and protein levels as well as TIMP1, TFF3 in mRNA levels in gastric cancer tissues. The data are the first study to demonstrate HIF-1α-regulated transcription factors and their corresponding network genes in gastric cancer. Further study with a larger sample size and more functional experiments is needed to confirm these data and then translate into clinical biomarker discovery and treatment strategy for gastric cancer.</p></div

Validation of overexpression of HIF-1α, TIMP1 and TFF3 in 10 pairs of gastric cancer vs. normal tissues.

<p>a and b, Detection of HIF-1α, TIMP1 and TFF3 mRNA expression in gastric cancer vs. normal tissues using PCR and qRT-PCR. Levels of HIF-1α, TIMP1, TFF3 mRNA were 2.55±0.56, 1.58±0.25, 2.16±0.59 folds up-regulated in tumor tissues, respectively compared to those of the normal ones. *p<0.01. c and d, Western blot analysis of HIF-1α protein. Tumor tissues expressed higher level of HIF-1α protein compared to the normal ones [p<0.01 (d). N, normal tissues; C, cancer tissues (c)].</p

TF-gene network of these 82 differentially expressed genes in gastric cancer tissues.

<p>Red circles in A are up-regulated genes, whereas green circles are down-regulated genes and the yellow triangles are these five key TFs. B, The brief framework of this network. The circles are the clustered genes and the number of genes is shown inside. The direction of the arrow is from the Source to the Target.</p

The hub genes are regulated by at least two TFs in this TF-gene regulatory network.

<p>Ellipses are hub genes that are regulated by transcription factors, the triangles are these five transcription factors in the TF-gene regulatory network.</p

The bi-clusters analysis of these 82 differentially expressed genes in TF-gene regulatory network.

<p>Each row represents a gene and each column represents a sample, the “C” columns at the bottom represent cancer tissues, “N” columns represent normal tissues. >1 Red for high expression in cancer compared to normal and <1 green for low expression in cancer compared to normal ones.</p

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Characteristics of the study group and healthy subjects.

<p>GFR, glomerular filtration rate; AST, glutamate oxaloacetate transaminase; ALT, glutamate pyruvate transaminase; L-FABP, liver-type fatty acid-binding protein; NGAL, neutrophil gelatinase-associated lipocalin; KIM-1, kidney injury molecule-1; NAG, N-acetyl-β-D-glucosaminidase; RBC, red blood cells; WBC, white blood cells.</p><p>Characteristics of the study group and healthy subjects.</p

Distribution of biomarker levels in the deteriorated renal function group and the stable group at 1-year follow-up.

<p>A. Distribution of 72-h postoperative uKIM-1 levels in the deteriorated renal function group and the stable group at 1-year follow-up. B. Distribution of preoperative uL-FABP levels in the deteriorated renal function group and the stable group at 1-year follow-up. C. Distribution of 48-h postoperative uL-FABP levels in the deteriorated renal function group and the stable group at 1-year follow-up. D. Distribution of 72-h postoperative uL-FABP levels in the deteriorated renal function group and the stable group at 1-year follow-up. E. Distribution of preoperative uNGAL levels in the deteriorated renal function group and the stable group at 1-year follow-up.</p

Comparison of the deteriorated renal function group and the stable group at 1-year follow-up.

<p>*The differences between the deteriorated renal function group and the stable group were statistically significant (P<0.05).</p