Serum Lipidomic Fingerprints Encode Early Diagnosis and Staging of Lung Cancer on a Novel PbS/Au-Layered Substrate

Lungcancer (LC) is a major cause of mortality among malignanttumors. Early diagnosis through lipidomic profiling can improve prognosticoutcomes. In this study, a uniform PbS/Au-layered substrate that enhancesthe laser desorption/ionization process, an interfacial process triggeredon the substrate surface upon laser excitation, was designed to efficientlycharacterize the lipidomic profiles of LC patient serum. By controllingthe stacking arrangement and particle sizes of PbS QDs and AuNPs,the optimized substrate promotes the generation of excited electronsand creates an enhanced electric field that polarizes analyte molecules,facilitating ion adduction formation ([M + Na](+) and [M+ K](+)) and enhancing detection sensitivity down to thefemtomole level. Combining multivariate statistics and machine learning,a distinct lipidomic biomarker panel is successfully identified forthe early diagnosis and staging of LC, with an accurate predictionvalidated by an area under the curve of 0.9479 and 0.9034, respectively.We also found that 18 biomarkers were significantly correlated withsix metabolic pathways associated with LC. These results demonstratethe potential of this innovative PbS/Au-layered substrate as a sensitiveplatform for accurate diagnosis of LC and facilitate the developmentof lipidomic-based diagnostic tools for other cancers.

Automated summary

In this study, a PbS/Au-layered substrate was designed to efficiently characterize the lipidomic profiles of lung cancer (LC) patient serum for early diagnosis. The optimized substrate promotes the generation of excited electrons and creates an enhanced electric field, facilitating ion adduction formation and enhancing detection sensitivity. Through multivariate statistics and machine learning, a distinct lipidomic biomarker panel is successfully identified for early diagnosis and staging of LC. This innovative substrate shows potential as a sensitive platform for accurate diagnosis of LC and development of lipidomic-based diagnostic tools for other cancers.