Taking advantage of specific alterations of DNA repair capacity in cancer cells may allow us to better match cancer patients with DNA damaging chemotherapeutic agents. This study is targeted to identify the occurrence of alterations of DNA repair genes in lung cancer  adenocarcinoma patients.
Gene expression of 200 DNA repair genes in 120 (110 adenocarcinoma and 10 normal lung) samples was profiled on the Nanostring nCounter platform. The data was normalized based on positive and internal (reference genes) controls. All source of unwanted variation were interrogated by the Surrogate Variable Analysis (SVA) method. Integrative analysis of DNA repair gene expression (RNAseqV2) and DNA methylation (Infinium 450k) was performed by using the TCGA datasets for lung adenocarcinoma. Differential methylated regions and differential expressed genes were interrogated by applying the limma and edgeR methods respectively.
Several DNA repair genes including MGMT, RAD23B, XRCC5 and XPA showed differential expression in cancer samples. These alterations may associate with clinical outcomes of current chemotherapy treatment but also indicate new modalities for therapy. The integrative analysis showed that DNA methylation affects the expression of some of the DNA repair genes. DNA methylation as a source of gene-specific biomarkers may have utility in guiding clinical decision making including the choice of chemotherapy.