Using proteomics and metabolomics to identify therapeutic targets for senescence mediated cancer: genetic complementarity method

BACKGROUND: Senescence have emerged as potential factors of lung cancer risk based on findings from many studies. However, the underlying pathogenesis of lung cancer caused by senescence is not clear. In this study, we try to explain the potential pathogenesis between senescence and lung cancer through proteomics and metabonomics. And try to find new potential therapeutic targets in lung cancer patients through network mendelian randomization (MR). METHODS: The genome-wide association data of this study was mainly obtained from a meta-analysis and the Transdisciplinary Research in Cancer of the Lung Consortium (TRICL), respectively.And in this study, we mainly used genetic complementarity methods to explore the susceptibility of aging to lung cancer. Additionally, a mediation analysis was performed to explore the potential mediating role of proteomics and metabonomics, using a network MR design. RESULTS: GNOVA analysis revealed a shared genetic structure between HannumAge and lung cancer with a significant genetic correlation estimated at 0.141 and 0.135, respectively. MR analysis showed a relationship between HannumAge and lung cancer, regardless of smoking status. Furthermore, genetically predicted HannumAge was consistently associated with the proteins C-type lectin domain family 4 member D (CLEC4D) and Retinoic acid receptor responder protein 1 (RARR-1), indicating their potential role as mediators in the causal pathway. CONCLUSION: HannumAge acceleration may increase the risk of lung cancer, some of which may be mediated by CLEC4D and RARR-1, suggestion that CLEC4D and RARR-1 may serve as potential drug targets for the treatment of lung cancer.