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Figure 1.

Rules and schematic diagram for the statistical model.

A. Rules for matching an edge of two adjacent entities in KEGG pathways with their gene expression changes. Given an edge, gene 1 is called a source node of which the edge goes out, and gene 2 a sink node of which the edge comes in. B. Schematic diagram of the statistical model. Given a subpathway, the longest segment (well-defined subpathway) from the leaf node was identified. A statistic S for the well-defined subpathway was calculated. The null distribution of S was obtained via 1,000,000 sample label permutations and the p-value for the observed S was finally calculated (see Materials and Methods for details). Red ovals are up-regulated in the cancer patients, and green ones down-regulated.

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Figure 2.

Overview of our study.

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Figure 3.

Mapping of the entries of the well-defined subpathways into the focal adhesion pathway.

If the fold-change of the cancer patient group over the healthy control group is greater than one the gene is red, otherwise green. See Table 1 and Table S1 for detailed information.

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Figure 4.

NK cell mediated cytotoxicity.

Same description as Figure 3.

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Table 1.

The gene entries of the well-defined subpathways used for visualizing the three pathways diagrams (Figures 3 and 4, Figure S3).

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Table 2.

The gene expressions of c-IAPs, survivin (BIRC5) and XIAP (BIRC4).

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Figure 5.

The association network of the susceptible gene set from Hong et al. and several representative genes from Table 1.

The three green boxes represent the gene set (CYR61, FOS, FOSB, UCHL1, VIP, EGR1, KRT24), NK cell mediated cytotoxicity (IFNG, FAS, FASLG), and Focal adhesion (PTK2) from left to right. The options used in the network are described in Figure S7. The pale blue-filled boxes represent Mesh (www.nlm.nih.gov/mesh/) Diseases terms for the genes. It is noted that ITGB5 associations did not appear in the PubGene result.

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Table 3.

The genes involved in immunosuppressive MDSCs and TReg cells in terms of immunosuppression.

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Table 4.

The genes involved in EMT.

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Figure 6.

Summary of functional roles of the predictor gene set in terms of EMT and immunosuppression.

The two elements (VIP, CYR61) of the predictor gene set can adjust the local immune system and induce malignant phenotype transformation via EMT.

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Figure 7.

The example of determination of the well-defined subpathway from a subpathway.

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