Integrating miRNAs and Bacterial DNA for Early Detection of Lung Cancer

Purpose The early detection is crucial for improved outcomes in lung cancer, which remains a leading cause of cancer-erelated deaths. There is an urgent need for precise molecular biomarkers to diagnose early-stage lung cancer. To address this, we assessed the potential of integrating diverse molecular biomarkers across both plasma and sputum to improve the accuracy of diagnosis, given the heterogeneous nature of lung cancer arising from multifactorial molecular aberrations. Methods We utilized droplet digital PCR to quantify miRNAs in plasma and bacterial DNA in sputum collected from 114 lung cancer patients and 121 cancer-free smokers. The participants were randomly divided into a development cohort and a validation cohort. Logistic regression models with constrained parameters were employed to optimize a signature with the highest sensitivity and specificity for early detection of lung cancer. Results The individual plasma miRNAs and sputum bacterial biomarkers had sensitivities of 62%-71% and specificities of 61%-79% for diagnosing lung cancer. A panel of plasma miRNA or sputum bacterial biomarkers produced sensitivities of 79%-85% and specificities of 74%-82%. An integrated signature comprising two miRNAs in plasma and three bacterial biomarkers in sputum was developed in the development cohort, and it exhibited a higher sensitivity (87%) and specificity (89%) in comparison to individual biomarkers. The signature’s diagnostic value was confirmed in the validation cohort, regardless of tumor stage, histological type, and demographic factors. Conclusion The integration of miRNA and bacterial biomarkers across both plasma and spu-tum samples offered an effective approach for the diagnosis of lung cancer. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: University of Maryland Baltimore Institutional Review Board I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript