Expression And Prognostic Role Of MDFI In NSCLC

Background and Objectives: Approximately 80% of lung cancers are classified as non-small cell lung cancer(NSCLC),with lung adenocarcinoma(LUAD)and lung squamous cell carcinoma(LUSC)being the predominant subtypes.The incidence and mortality of lung cancer are continuously rising,creating a significant economic burden.Lung cancer is the leading cause of cancer-related deaths in men aged ≥40 years and women aged ≥60 years.Targeted therapies for lung cancer have been developed through the examination of genetic drivers associated with malignancy,resulting in the creation of clinically relevant targeted drugs.As a result,identifying new targets for the treatment of lung cancer has become crucial.The myogenic differentiation family inhibitor(MDFI)is a significant transcription factor that plays a role in the cytoplasmic retention of Myod family members by masking their nuclear localization signal and interfering with their DNA binding activity.MDFI also plays an important role in trophectoderm and cartilage differentiation,regulates TCF7L1/TCF3 transcriptional activity by directly interacting with TCF7L1/TCF3 and preventing DNA binding,and affects axin regulation of the WNT and JNK signaling pathways through its binding to the axin complex,resulting in elevated levels of free β-linked protein.The role of MDFI in NSCLC and its impact on prognosis,especially in LUAD,is not yet fully understood.This study aimed to investigate the mechanism of MDFI in NSCLC and its effect on prognosis.Methods: Data on LUAD were obtained from the Cancer Genome Atlas(TCGA)and the Gene Expression Omnibus(GEO),analyzed and visualized using the R programming language.A logistic regression analysis was performed to evaluate the relationship between clinical information and expression of MDFI in LUAD,with two sets of tissue microarrays(TMAs)further supporting the overexpression of MDFI in LUAD and its impact on patient prognosis.The correlation between MDFI and immune infiltration was also investigated.The biological effects of MDFI on LUAD tumor cells were analyzed through Gene Set Enrichment Analysis(GSEA)and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(GO/KEGG)analysis.The difference in tumor mutation burden(TMB)was assessed between high and low expression groups of MDFI and patient survival was analyzed based on MDFI levels.Finally,the DSigDB database was utilized to predict drugs that may have efficacy against MDFI.Results: Our analysis of the TCGA dataset revealed a significantly higher expression of MDFI in LUAD tissues(P < 0.001).The K-M survival analysis showed that LUAD patients with high MDFI expression had a poorer prognosis(P < 0.001),which was further confirmed by TMA in both groups(P = 0.024).Logistic regression analysis revealed that MDFI was an independent predictor and was associated with poor prognosis in LUAD(P <0.001,P =0.021).Our study also found a significant association between MDFI expression and effector memory CD8 T cells and monocytes.Co-expression analysis of genes closely linked to MDFI expression revealed five prominent genes,such as TNS4 and ITGB4.The somatic mutation analysis showed a lower number of mutations in the MDFI low expression group compared to the high expression group.Evaluation of clinical characteristics,TMB and Tumor Microenvironment(TME)in the high and low expression score groups revealed that the low risk group had lower TMB(P < 0.001),a more abundant immune cell infiltration,and a better prognosis.Conclusion: The present study investigated the expression and prognostic significance of MDFI in patients with LUAD,a subtype of NSCLC.Results showed that MDFI was highly expressed in LUAD tissues and significantly associated with poor prognosis,as demonstrated by Kaplan-Meier survival analysis and logistic regression analysis.Furthermore,our study showed that MDFI was associated with immune infiltration in LUAD and could play a role in tumor proliferation and spread.These findings suggest that MDFI could serve as a potential novel biomarker for the diagnosis and prognosis of LUAD,and that testing for MDFI expression may provide early diagnosis and treatment opportunities for patients with NSCLC.By utilizing more precise therapeutic strategies based on MDFI expression levels,patients with LUAD may benefit from improved outcomes in the clinical setting.