Four and a half LIM domain protein 1 as a Novel Prognostic Biomarker and Correlation with Immune Infiltration Levels in Lung Adenocarcinoma

Background: We aimed to investigate the prognostic value of Four and a half LIM domain protein 1 (FHL1) and its correlation with FHL1 and tumor-infiltration immune cells (TIICs) in lung adenocarcinoma (LUAD). Methods: FHL1 expression status and its influence on clinical characteristics in LUAD and Lung squamous cell carcinoma (LUSC) were collected based on GEPIA, TCGA, GEO, CPTAC, the HPA database, and the GTEx Portal. The ROC curve and Kaplan-Meier plots were used to assess the value of FHL1 expression levels in the diagnosis and prognosis of LUAD and LUSC. The interaction network revealed the related genes and proteins of FHL1 by GeneMANIA and STRING. The functional enrichment analysis based on FHL1 and FHL1-related differentially expression genes (DEGs) was conducted by the “clusterProfile” package and Metascape, respectively. The correlation analysis between FHL1 expression and tumor immunity was performed using TISIH, TIMER, and TISIDB. cBioPortal was used to investigate the mutation status between FHL1 and representative immune checkpoints. Results: The results showed that FHL1 expression was significantly lower in tumors relative to adjacent standard samples, and downregulated FHL1 predicted a worse prognosis for LUAD than that for LUSC. Additionally, FHL1 participated in the interleukin 15 mediated signaling pathway, response to interleukin-9, and neutrophil-mediated cytotoxicity. It was also positively correlated with TIICs (B cells, CD8+T, CD4+T cells, macrophages, neutrophils, and DC), immune checkpoints (CD80, CD48, VTCN, and PVR), and chemokines (CCL5, CCL17, CCL20 and CXCL8). Conclusion: FHL1 is a powerful prognostic biomarker of immune infiltration.