Bioinformatics reveals the prognostic potential of manganese metabolism-related genes in lung adenocarcinoma.

Manganese metabolism may be involved in the malignant progression of lung adenocarcinoma (LUAD). Clarifying the roles of manganese metabolism-related genes (MMRGs) in LUAD may provide potential therapeutic targets for LUAD treatment. Mendelian randomization analysis and machine learning methods were applied to analyze transcriptome data for screening prognosis-related genes in LUAD. Subsequently, a risk model was constructed and a nomogram was plotted. Meanwhile, a series of analyses were carried out focusing on the immune microenvironment, drug sensitivity, and the single-cell level. Finally, the expression of relevant proteins was further verified by combining RT-qPCR and Western Blot. We have screened out six risk genes for LUAD: TXNRD1, CDKN3, BTG2, SELENBP1, DTYMK, and CHEK1. Subsequently, a risk model was constructed, which effectively predicts the survival of LUAD patients. Gene Set Enrichment Analysis (GSEA) revealed that these six genes may be involved in the regulation of the cell cycle in LUAD. In addition, they may modulate the tumor immune microenvironment and induce resistance to chemotherapeutic drugs. RT-qPCR and Western Blot confirmed low BTG2 and SELENBP1 and high CDKN3, CHEK1, DTYMK, and TXNRD1 expression in LUAD tissues and cell lines. Our study indicates that TXNRD1, CDKN3, BTG2, SELENBP1, DTYMK, and CHEK1 may be important biomarkers for the prognosis of LUAD, providing potential approaches for prognostic evaluation and medication strategies in LUAD.