Upregulation of the tumor suppressor gene enhances tumorigenesis and predicts poor prognosis of lung adenocarcinoma.

BACKGROUND

, a gene associated with various cancers, is considered a tumor suppressor. However, the role of in lung adenocarcinoma (LUAD) remains unknown. In this study, we aimed to assess the role of in the occurrence and prognosis of LUAD.

METHODS

Using three-tier HTSeq count RNA sequencing data from The Cancer Genome Atlas, we assessed LIN9 expression for the LUAD dataset using the DESeq2 R package and RT-qPCR experiments. Biological functions were assessed using gene set enrichment analysis (clusterProfiler and GOplot). The expression of and the infiltration of immune cells were assessed by Single-sample gene set enrichment analysis. We conducted correlation study using clinical characteristics and receiver operating characteristic curve analysis. The predictive value of was determined using univariate and multivariate Cox regression as well as Kaplan-Meier analysis. Additionally, functional studies were conducted to validate its role in the progression of LUAD.

RESULTS

Expression of was significantly elevated in LUAD, primarily influencing cell cycle, division, and signaling pathways. High expression correlated positively with the infiltration of Th2 cells and inversely with that of plasmacytoid dendritic cells. Furthermore, was associated with older age and advanced clinical stages, posing risks to overall, progression-free, and disease-specific survival. served as a good diagnostic marker, particularly in females, patients aged over 65, and those with clinical N1-3 and M1 stages. Elevated expression enhanced proliferation, migration, and invasion of LUAD cells.

CONCLUSION

High expression potentially contributes to LUAD occurrence through cell cycle regulation and chromosomal modification. It promotes the malignant characteristics of LUAD cells and holds prognostic value for affected patients.