This study investigates the role of the *NR5A2* gene in lung adenocarcinoma (LUAD) by analyzing its expression and impact on cancer stem cells (CSCs) through bioinformatics methods. The authors used the One-Class Linear Regression (OLCR) algorithm and immune scoring systems to explore the regulatory mechanisms of *NR5A2* on CSC activity and its effect on overall survival. Key findings include: 1. **Expression and Prognosis**: *NR5A2* expression was significantly lower in LUAD tissues compared to normal lung tissues, and its decreased expression was associated with shorter overall and progression-free survival in LUAD patients. 2. **CSC Regulation**: *NR5A2* may regulate LUAD CSCs through selective splicing mutations, affecting tumor growth, self-renewal, and drug resistance. 3. **SNP Pathway**: The study identified that *NR5A2* mutations, particularly single nucleotide polymorphisms (SNPs), are significant in LUAD CSCs, influencing immune cell infiltration and drug resistance. 4. **Prognostic Model**: A nomogram was developed to predict 1-, 3-, and 5-year overall recurrence rates based on *NR5A2* expression and patient age, showing good agreement between predictions and actual observations. 5. **Biological Functions**: GO and KEGG analyses revealed that *NR5A2* is involved in cell division, drug resistance, and apoptosis pathways, which indirectly affect the survival prognosis of LUAD patients. 6. **Clinical Implications**: The study highlights the potential of *NR5A2* as a therapeutic target and a prognostic marker for LUAD, providing new insights into the molecular mechanisms of LUAD and potential therapeutic strategies. The study concludes that *NR5A2* plays a crucial role in regulating CSC activity and overall survival in LUAD, offering a new perspective for understanding and treating this disease.This study investigates the role of the *NR5A2* gene in lung adenocarcinoma (LUAD) by analyzing its expression and impact on cancer stem cells (CSCs) through bioinformatics methods. The authors used the One-Class Linear Regression (OLCR) algorithm and immune scoring systems to explore the regulatory mechanisms of *NR5A2* on CSC activity and its effect on overall survival. Key findings include: 1. **Expression and Prognosis**: *NR5A2* expression was significantly lower in LUAD tissues compared to normal lung tissues, and its decreased expression was associated with shorter overall and progression-free survival in LUAD patients. 2. **CSC Regulation**: *NR5A2* may regulate LUAD CSCs through selective splicing mutations, affecting tumor growth, self-renewal, and drug resistance. 3. **SNP Pathway**: The study identified that *NR5A2* mutations, particularly single nucleotide polymorphisms (SNPs), are significant in LUAD CSCs, influencing immune cell infiltration and drug resistance. 4. **Prognostic Model**: A nomogram was developed to predict 1-, 3-, and 5-year overall recurrence rates based on *NR5A2* expression and patient age, showing good agreement between predictions and actual observations. 5. **Biological Functions**: GO and KEGG analyses revealed that *NR5A2* is involved in cell division, drug resistance, and apoptosis pathways, which indirectly affect the survival prognosis of LUAD patients. 6. **Clinical Implications**: The study highlights the potential of *NR5A2* as a therapeutic target and a prognostic marker for LUAD, providing new insights into the molecular mechanisms of LUAD and potential therapeutic strategies. The study concludes that *NR5A2* plays a crucial role in regulating CSC activity and overall survival in LUAD, offering a new perspective for understanding and treating this disease.