Identification of Clinical Prognostic Regulators and Analysis of Ferroptosis-Related Signatures in the Tumor Immune Microenvironment in Lung Squamous Cell Carcinoma.

OBJECTIVE: Lung squamous cell carcinoma (LUSC) is a common respiratory malignancy and presents an increasing prevalence. Ferroptosis is a newly identified controlled cell death that has captured clinical attention worldwide. However, the ferroptosis-related lncRNA expression in LUSC and its relevance to prognosis remain elusive.

METHODS: The research measured predictive ferroptosis-related lncRNAs in LUSC samples from the TCGA datasets. Data on the stemness indices (mRNAsi) and corresponding clinical characteristics were obtained from TCGA. A prognosis model was established using the LASSO regression. Changes within the neoplasm microenvironment (TME) and medicine association were examined to grasp higher immune cell infiltration in numerous risk teams. In line with coexpression studies, the expression of lncRNAs is closely associated with that of ferroptosis. They were overexpressed in unsound people in the absence of alternative clinical symptoms.

RESULTS: The low-risk and speculative teams were considered to have substantial differences in CCR and inflammation-promoting genes. C10orf55, AC016924.1, AL161431.1, LUCAT1, AC104248.1, and MIR3945HG were highly expressed in the high-risk group, suggesting their involvement in the oncology process of LUSC. Moreover, AP006545.2 and AL122125.1 were considerably higher in the low-risk group, implying the potential of these genes as LUSC tumor suppressor genes. The biomarkers listed above may serve as therapeutic targets for LUSC. lncRNAs were also linked to patient outcomes in the LUSC trial.

CONCLUSION: lncRNAs of ferroptosis were overexpressed in the high-risk cohort without other clinical signs, implying their potential to predict BLCA prognosis. GSEA highlighted immunological and tumor-related pathways in the high-risk group. LUSC occurrence and progression are linked to lncRNAs of ferroptosis. Corresponding prognostic models help forecast the prognosis of LUSC patients. lncRNAs of ferroptosis and associated immune cell infiltration in the tumor microenvironment (TME) may serve as potential therapeutic targets in LUSC, which requires further trials. In addition, the lncRNAs of ferroptosis signature offer a viable alternative to predict LUSC, and these ferroptosis-lncRNAs show a prospective research area for LUSC-targeted treatment in the future.