“SMART” digital nucleic acid amplification technologies for lung cancer monitoring from early to advanced stages

Recently, liquid biopsy based on detection of circulating nucleic acid (NA) biomarkers from body fluids has emerged as a promising strategy for lung cancer monitoring. Considering extremely low abundance of circulating NA in body fluids and the interference of normal cell-free NA, digital NA amplification (digital NAA) technologies ( i.e. , digital polymerase chain reaction and digital isothermal amplification) with high sensitivity and specificity have been demonstrated to be well suited for early diagnosis, minimal residual disease detection, prognosis prediction and companion diagnosis of lung cancer. In this paper, we firstly summarized the evolution of digital NAA technologies. On this basis, we proposed “ SMART ” ( i.e. , S uper-fast, M ultiplex, A utomated, integ R a T ed) digital NAA technologies for accelerating wider applications in lung cancer monitoring. Then, the existing NA biomarkers at different stage of lung cancer were summarized, and existing digital NAA methods for detecting these biomarkers were introduced. Finally, conclusions and future perspectives were proposed. • “ SMART ” ( S uperfast, M ultiplex, A utomated, integ R a T ed) digital nucleic acid amplification technologies are proposed. • Different leading nucleic acid biomarkers at different stages of lung cancer are summarized. • Nucleic acid biomarkers for early detection of lung cancer are compared from the aspect of stability, sensitivity, specificity and panel size. • Existing digital NAA technologies employed for lung cancer monitoring have been summarized.