RNF213 gene mutation of circulating tumor DNA in early diagnosis of NSCLC using targeted next-generation sequencing

Introduction: To distinguish early stage lung cancer from benign disease of the lung nodules, especially the lesions with ground-glass opacity (GGO) or ground-glass nodule (GGN), we assessed gene mutations of the ctDNA in peripheral blood by using targeted next-generation sequencing (NGS). Methods Single lung nodule patients without mediastinal lymph nodes or symptoms hardly diagnosed by chest CT and biomarker of lung cancer were enrolled. All patients received minimally invasive surgery but refused preoperative biopsy. Gene mutations of pre-operative blood samples were detected by targeted NGS. Mutations with statistical differences were screened in lung cancer and benign disease grouped by postoperative pathology. Gene expression was determined by immunohistochemistry. Highly expressed genes were selected as biomarkers to verify the mutations in peripheral blood. Results In training set, RNF213, KMT2D, CSMD3 and LRP1B genes mutated more frequently in early stage lung cancer (25cases) than benign nodules (18cases) (P<0.05). High expressions of RNF213 gene in lung cancers and low expressions in benign diseases were evaluated by immunohistochemistry. RNF213 gene mutated in 25% lung cancer samples in the validation set of 28 samples and showed high specificity (100%) and low sensibility (25.9%). In GGO and GGN patients, RNF213 mutated more frequently in early stage lung cancer compared to benign diseases (P<0.05). Conclusions RNF213 gene mutation was observed more frequently in early stage lung cancer, but rather than benign nodules. Mutation of RNF213 gene in peripheral blood may be a high specificity biomarker and valuable for early diagnosis of lung cancer.