Fig. 2

The methylation and expression profiles of NTRKs gene in CRC. a–c. The distribution and correlation of methylation and expression profiles of NTRK1, NTRK2 and NTRK3 gene in CRC and normal mucosa tissue. The heatmaps showed the results of probe-dimensional hierarchical clustering analysis of FHCRC cohort based on β values of all probes within NTRK1 (a, left), NTRK2 (b, left), and NTRK3 (c, left). Each row represented a probe and each column represented a CRC or normal mucosa sample in the heatmap. Probes targeting promoter region were annotated on heatmap left. The red lines annotated in the heatmap for NTRK3 indicated cg27034819 (top) and cg11525479 (bottom). NTRKs gene expression signature in each cohort showed suppressed mRNA expression of NTRK2 (b, middle) and NTRK3 (c, middle) in CRC tissues compared with normal mucosa tissue. Differences between CRC tissue and normal mucosa tissue were assessed with student t-test, and P values summarized with asterisks were shown in the upper space of the plot (***P < 0.001). The Spearman correlation analysis between mean promoter methylation of gene expression in each NTRK gene was shown in right panel. d Volcano plot of statistical significance against hazard ratio for DFS among all CpG sites within NTRKs gene targeted by 450K microarray probes. The top-ranked significantly probe was annotated according to the P values in the univariate Cox analyses. See Additional file 1 for the full results of univariate Cox analysis relevant to this panel. e. A QMSP assay was developed using primers and probe targeting cg27034819–cg11525479 region