Circulating Bacterial DNA as Plasma Biomarkers for Lung Cancer Early Detection

SIMPLE SUMMARY: Pathogenic bacteria play a crucial role in tumor development. Our study analyzed the presence of bacteria related to lung cancer in lung tumors, normal lung tissues, and plasma from lung cancer patients. Three bacteria (Selenomonas, Streptococcus, and Veillonella) showed consistent changes in plasma and higher DNA abundances in the plasma of cancer patients compared with healthy controls. The use of these three bacteria as a plasma biomarker panel can identify lung cancer, regardless of histology and stage. Our findings were validated in additional clinical specimens, demonstrating the potential of circulating bacterial DNA as plasma biomarkers for lung cancer. ABSTRACT: Lung cancer is a leading cause of cancer deaths and early diagnosis can significantly improve outcomes. Pathogenic bacteria have been shown to play a role in tumorigenesis and its analysis provides a new approach for cancer diagnosis. To evaluate the potential of bacteria as plasma biomarkers for early lung cancer detection, we analyzed eight lung-cancer-related bacterial genera in 58 lung cancer patients and 58 controls using ddPCR. Our results showed that five genera had higher DNA abundance in lung tumor tissues compared with normal tissues. Three of these genera (Selenomonas, Streptococcus, and Veillonella) displayed consistent changes in plasma, with higher DNA abundance in lung cancer patients compared with controls. When used as a panel, these three bacterial genera had a sensitivity of 75% and specificity of 78% for lung cancer detection, regardless of stage or histology. The performance of this biomarker panel was confirmed in an independent cohort of 93 lung cancer cases and 93 controls. Thus, circulating bacterial DNA has the potential to be used as plasma biomarkers for early lung cancer detection.