Kaplan-Meier curves for breast cancer patients from validation cohort grouped by lymph node status.

<p>Red curves are for VAG-positive patients while blue curves are for VAG-negative patients. VAG-positive patients were defined as those having a risk score greater than the group median. <i>P</i>-values were calculated by log-rank tests for the differences in survival between VAG-positive and -negative groups.</p

<i>VDAC1</i> associated gene signature (VAG).

<p><i>VDAC1</i> associated gene signature (VAG).</p

Kaplan-Meier curves for patients in the validation cohorts.

<p>The expression of VAG predicts poor recurrence-free survival in breast, colon, and lung cancers. Red curves are for VAG-positive patients while blue curves are for VAG-negative patients. VAG-positive patients were defined as those having a risk score greater than the group median. <i>P</i>-values were calculated by log-rank tests for the differences in survival between VAG-positive and -negative groups.</p

<i>VDAC1</i> and its interacting genes.

<p>(A) <i>VDAC1</i> is up-regulated in tumor tissues in breast, colon, liver, lung, pancreatic, and thyroid cancers. Paired normal and tumor tissues were included in the comparison. Y-axis: log₂-transformed expression values. (B) The top 10 GO biological process terms associated with dysregulated <i>VDAC1</i> interacting genes. Forty-four <i>VDAC1</i> interacting genes were identified as being commonly differentially expressed between normal and tumor tissues in human carcinomas. The <i>P</i>-values were calculated by Fisher’s exact test. The red dash line denotes the significance level of 0.05. (C) The top ten PANTHER pathway terms associated with dysregulated <i>VDAC1</i> interacting genes. The <i>P</i>-values were calculated by Fisher’s exact test. The red dash line denotes the significance level of 0.05.</p

Multivariate Cox proportional hazards regression of survival in the validation cohorts.

<p>Multivariate Cox proportional hazards regression of survival in the validation cohorts.</p

Non-random prognostic power of VAG in breast, colon, and lung cancers.

<p><i>Z</i> denotes the Wald statistic, the ratio of Cox regression coefficient to its standard error. The black triangles stand for the <i>Z</i> values of VAG. The grey areas show the distribution of <i>Z</i> values for the 1,000 resampled gene signatures with identical size as VAG under the null hypothesis of no association between VAG and recurrence-free survival. One-tailed <i>P</i>-values for the right tail of the sampling distribution were calculated.</p

Kaplan-Meier curves for colon cancer patients from the validation cohort stratified by stage.

<p>Red curves are for VAG-positive patients while blue curves are for VAG-negative patients. VAG-positive patients were defined as those having a risk score greater than the group median. <i>P</i>-values were calculated by log-rank tests for the differences in survival between VAG-positive and -negative groups.</p

Cox proportional hazards regression of survival by VAG status in breast, colon, and lung cancers.

<p>Cox proportional hazards regression of survival by VAG status in breast, colon, and lung cancers.</p

Non-Silent Story on Synonymous Sites in Voltage-Gated Ion Channel Genes

<div><p>Synonymous mutations are usually referred to as “silent”, but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are associated with transmembrane or channel-forming regions, i.e., the sites that are particularly likely to be involved in the closing and opening of an ion channel. Our hypothesis is that translationally optimal codons are preferred at the sites within transmembrane domains or channel-forming regions in voltage-gated ion channel genes to avoid mistranslation-induced protein misfolding or loss-of-function. Using the Mantel-Haenszel procedure, which applies to categorical data, we found that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in voltage-gated ion channel genes are not neutral. Silent mutations at channel-related sites may lead to dysfunction of the ion channel.</p> </div

Comparison in gene expression level between normal and tumor tissues.

a<p>Fold change is calculated by dividing the expression of tumor tissue by the expression of normal tissue.</p>b<p><i>P</i>-value is calculated by paired t-test and adjusted by Benjamini & Hochberg correction.</p