LAYN is Correlated with Immune Infiltration, Cancer Associated Fibroblasts and Prognosis in Bladder Cancer

Abstract Background LAYN is a novel gene in liver cancer, non-small cell lung cancer and colorectal cancer for its diverse functions in tumor microenvironment (TME). However, the role of LAYN in shaping the TME remains to be elucidated in bladder cancer (BLCA). Methods Datasets (including RNA-sequencing, single-cell RNA-sequencing and survival data) were obtained from public databases. The correlation of LAYN with TME was analyzed with Tumor Immune Estimation Resource (TIMER) site. Immunohistochemistry from a single institution was used to verify the relationship between LAYN expression and TME marker levels and the efficacy of immunotherapy. Results Enrichment analysis revealed that LAYN overexpression was associated with the regulation of immune infiltration and cancer-associated fibroblasts (CAFs) pathways and functions in BLCA. Notably, LAYN overexpression led to increased immune infiltration but also an exhausted TME according to the correlation analysis of immune cells such as CD8 + T cells, CD4 + T cells, immune-related markers, and CAF-related markers in the TCGA database. These findings were validated by immunohistochemistry at a single institution. Furthermore, higher LAYN expression levels were associated with worse survival in the TCGA dataset, the IMvigor210 dataset and the cohort from our center. Additionally, LAYN, TIM-3, FOXP3 and FAP were linked to poor outcomes in patients treated with immunotherapy. Conclusions Our study revealed a correlation between high LAYN expression and abundant immune infiltration and CAFs in BLCA. However, LAYN may play a role in the regulation of immune suppression and escape and could serve as a potential predictive marker for immune checkpoint inhibitor response and patient survival in BLCA.