Background: Lung cancer is the most frequent cancer globally with a high number of cancer-related deaths. The 4-and-a-half LIM domain protein 2 (FHL2) is an oncogenic gene, which promotes the proliferation, invasion, and metastasis of cancer cells. In this study, we aimed to demonstrate that lung cancer patients with high FHL2 expression have worse overall survival (OS) and relapse-free survival (RFS).

Methods: TCGA was used to study FHL2 mRNA expression. Nomograms were used to predict the relationship between FHL2 expression levels and survival. The qRT-PCR was used to detect the FHL2 expression in lung cancer cells. In vitro experiments including CCK-8 assay, wound healing, and Transwell assay were performed.

Results: This study comprised RNA-Seq gene expression data and clinical features for 1018 lung cancer patients. FHL2 was found to be overexpressed in lung cancer tissues. FHL2 demonstrated moderate diagnostic ability for lung cancer (AUC = 0.857). Kaplan–Meier curves and Cox regression analysis revealed the higher FHL2 expression with the poorer OS and RFS (P < 0.001). The nomogram results indicated that FHL2 could be used to predict the survival of lung cancer patients. GSEA analysis results show that high expression of FHL2 is related to glycolysis and unfolded protein reflection. FHL2 was highly expressed in lung cancer cells and related to their proliferation, migration, and invasion ability.

Conclusions: The high expression level of FHL2 in lung cancer can be used as an independent predictor of prognosis in clinical practice.