Genomic CpG methylation and TKI-response of the patient with advanced stage lung adenocarcinoma

The DNA methylation signature involved 87 differentially methylated regions (DMR) that distinguished patients’ response to EGFR-TKIs. The methylation level of HOXB9 (cg13643585) which was negatively correlated with gene expression and annotated as function of transcription factor displayed 88% and 92% of sensitivity with respect to objective response rate (ORR, OR=9.25, p=0.0002) and disease control rate (DCR, OR=6.64, p=0.0009), respectively. Importantly, HOXB9 gained methylation in patients with progressive disease (PD) relative to partial response (PR) patients specific to those who harbored EGFR-activating mutations (ORR, OR=8.8, p=0.0045; DCR, OR=6.63, p=0.018). The study population consisted of patients with advanced lung adenocarcinoma (stage IIIA to IV) who had received TKI therapy (Table 1) at the Taichung Veterans General Hospital (TCVGH) and National Taiwan University Hospital (NTUH). Fifty patients carried EGFR-activating mutation tumors (28 L858R/L861Q, 20 exon 19 deletion, 2 G719X) and 29 patients were wild type EGFR.