Lymphocyte Antigen 9 as a potential immunotherapeutic target and a new prognostic biomarker for lung adenocarcinoma

Abstract BackgroundLymphocyte Antigen 9 (LY9) participates in the development of several tumors and diseases. However, it has not been reported yet in lung adenocarcinoma (LUAD). MethodsFirst, we retrieved the pan-cancer transcriptomic and clinical data from the UCSC official website and performed LY9 differential expression analysis. Then, we used the Kaplan-Meier Plotter and GEPIA databases to perform prognostic analysis of LY9 expression in pan-cancer. Additionally, we conducted correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSOFT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9. Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis. Finally, we collected LUAD tissues for Quantitative Real-time PCR to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. ResultsResults showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD promotes the infiltration of multiple immune cells, while significantly and positively correlating with immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, the qRT-PCR results verified that the expression of LY9 in LUAD has a strong and positive correlation with CD4 and CD8 T cells. ConclusionSo LY9 can be a new prognostic biomarker and immunotherapeutic target for LUAD.