Correlation of gene copy number and corresponding gene expression values.

<p>Density analysis of the externally centered correlation coefficient (ECCC) log transformed (blue) mRNA expression values for all NSCLC cases (A), adenocarcinomas (B) and squamous cell cancer cases (C). The line forming a Gauss curve illustrates correlation values of randomly generated data. Randomization was achieved by permutation of gene copy number/mRNA pairs.</p

Impact of gene copy number and gene expression on survival.

<p>The plot shows the number of probe sets in relation to the AUC as a measure of survival association for gene copy number (red) and gene expression values (blue) in the complete set of NSCLC (A), adenocarcinomas (B) and squamous cell cancer (C). Considering all 39,788 matched copy number/RNA pairs it is evident that RNA levels exert a higher prognostic impact than gene copy number in the total group and in adenocarcinomas, while a similar influence of RNA levels and gene copy number is seen in squamous carcinomas. The red and blue strokes at the x-axis represent genes with highest externally centered correlation coefficients (ECCC>0.7, FDR adj. p<0.05).</p

Gene copy number changes of non-small cell lung carcinomas.

<p>Copy number (CN) call frequencies are given for all NSCLC cases (A), adenocarcinomas (B) and squamous cell cancer (C). The frequency plots (upper graphs) give the proportion of cases with loss and gain for each chromosomal position. Positions of selected genes (ERBB4, FHIT, APC, EGFR, MET, PTEN, LRP1, ERBB2, CCNE1) were highlighted in red.</p

Correlation between gene copy number and corresponding gene expression values over all chromosomes.

<p>(A) The modified Manhattan plot gives the median (red line) of the externally centered correlation coefficient (ECCC) and the 5% and 95% quantile (black lines) along all chromosomal positions. The black dots indicate the probe sets with highest ECCC (ECCC>0.7, FDR adj. p<0.05). The triangles show the position of hotspot regions. High correlation between copy number variation and gene expression is not randomly distributed over the genome but mostly occurs within specific chromosomal regions (hotspots). (B) Example of the hotspot region on chromosome 1p35-1p34 comprising 185 genes (gray bars) with 17 highly correlating genes (red bars). Each dot represents the ECCC of a probe set based on the analysis of all 190 NSCLC cases.</p

Highly correlating genes and association with survival.

<p>The meta-analysis of 10 NSCLC cohorts revealed that 70 of 440 highly correlating genes were associated with survival. For illustration three of the 70 genes are shown: CCT2, NUP107 and CAND1. The correlation between copy number and gene expression is shown by scatter plots (left). Survival time is visualized by Kaplan Meier plots (two panels in the middle). Patients were dichotomized at the 75% percentile for copy number (middle, left) and gene expression (middle, right). The forest plots illustrate the results of the meta-analysis including nine independent data sets and the Uppsala cohort (right).</p

Top 25 probe sets with highest ECCC of gene copy number levels and mRNA expression for tumors from 190 NSCLC patients.

<p>Top 25 probe sets with highest ECCC of gene copy number levels and mRNA expression for tumors from 190 NSCLC patients.</p