1076-Genetic Regulation in Lung Cancer susceptibility

The researchers established LungSCeQTL, the most extensive atlas of single-cell expression quantitative trait loci for human lung tissue to date, profiling over 222 donors. By utilizing scRNA-seq, the study demonstrates that over 60% of genetic regulatory signals are unique to specific cell types and frequently obscured in traditional bulk tissue analyses. Integrating these findings with lung cancer GWAS data pinpointed epithelial (AT2) and macrophage cells as primary drivers of inherited risk. The investigation successfully nominated 52 candidate genes for lung cancer, including 24 novel targets such as DLX3 and CLDN18. Functional experiments further validated DLX3's role in promoting oncogenic cellular states, offering potential new pathways for therapeutic intervention. This resource provides a vital framework for understanding how cell-specific genetic variation contributes to lung cancer susceptibility.

References:

• Fu Y, Wang Y, Jin C, et al. Single-cell eQTL mapping reveals cell-type-specific genetic regulation in lung cancer[J]. Cell genomics, 2026, 6(3).