Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression

Figures

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  Scheme 1. Step-by-step data analysis workflow designed for data mining approach

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  Fig. 1. Transcriptional profiling of key genes a OPN/SPP1; b APLN; c OPG/TNFRSF11B; d BAX; e Bcl-2; f CASP-3; g NOTCH-1; h NPTX2 and i PTX3 in hepatic biopsies of healthy donors (light grey box-plots) and recipients (dark grey bar box-plots) patients. Each box consists of five horizontal lines displaying the 10th, 25th, 50th (median), 75th, and 90th percentiles of the variable. All values, above the 90th percentile and below the 10th percentile, are plotted separately

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  Fig. 2. Interaction network of the key genes by GeneMANIA. The initial list of targeted genes and the type of connections between genes/proteins are illustrated in the network legend. In particular are depicted 9 nodes representing the key genes (light red dot); 20 critical interacting molecules (black dot) and 337 edges/links (purple: co-expression; cyan: pathway; green: genetic interactions). The 8 most representative critical interacting molecules were evidenced in light yellow. (Color figure online)

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  Fig. 3. Box plot of key gene mRNA expression using GEPIA database in liver hepatocellular carcinoma (LIHC/HCC) patients: a OPN; b APLN; c BAX; d CASP-3; e Bcl-2; f NOTCH-1; g OPG; h NPTX2; i PTX3. Red boxplot: tumor tissues (n = 369); grey box plot: normal tissues (n = 160). (Color figure online)

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  Fig. 4. validation of hub genes prognostic values by GEPIA database. Overall survival (OS) curves for a OPN; b APLN; c BAX; d OPG; e NPTX2; f CASP-3; g PTX3; h NOTCH-1; i Bcl-2 in all cases of LIHC. Survival curves marked as complete lines, and 95% confidence interval of survival curves marked as dotted lines. Red represents high expression and blue represents low expression. (Color figure online)

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  Fig. 5. a Heat map showing the expression level of the key (OPN; APLN; BAX; OPG; NPTX2; CASP-3; PTX3; NOTCH-1; Bcl-2) in LIHC, and normal hepatic tissue based on TCGA normal and GTEx data analyzed by GEPIA web server. The T represents LIHC tumor tissues and the N represents normal liver tissue. Light green: low expression, dark green: higher expression rate. b Transcript levels of key genes in LIHC analyzed with HCCDB generating a multi-gene summary. Threshold setting: p value: 0.05; fold change: all; gene rank: top 10%. Red represents upregulation (unfavourable) and blue represents downregulation (favorable). The numbers in the coloured cells represent the numbers of dataset meeting the threshold. Each label indicates: Diff: the number of differentially expressed datasets; Prognosis: the number of significant datasets by survival analysis; HCC/AllTumor: Red/Blue for positive/negative fold change in log2 scale by comparing HCC with all tumors (TCGA data); HCC/AllAdjacent: Red/Blue for positive/negative fold change in log2 scale by comparing HCC with all adjacent samples (TCGA data); HCC/Adjacent: Red/Blue for positive/negative fold change in log2 scale by comparing HCC with adjacent…

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  Fig. 6. expression of key genes based on sample type and apoptotic process performed with the UALCAN database in LIHC (Liver hepatocellular carcinoma). a BAX; b Bcl-2; c CASP-3 Red boxplot: primary tumor tissues (n = 371); blue boxplot: normal tissues (n = 50). Besides a table reporting the expression value related to median, upper/lower quartile and maximum/minimum (TPM) of each gene analysed. (Color figure online)