Expression And Prognostic Value Of NUSAP1 In Lung Adenocarcinoma

Objective:Lung adenocarcinoma(LUAD)is one of the common types of cancers of the respiratory system,with high mortality and recurrence rates,and a lack of reliable biomarkers at the clinical level to guide early clinical diagnosis and prognostic assessment,among others.There is increasing evidence that nucleolar and spindle-associated protein 1(NUSAP1)plays an important role in tumorigenesis and progression and is inextricably linked to its poor clinical prognosis,but the exact role and potential mechanisms of NUSAP1 in patients with LUAD are not yet clear.Therefore,this study aims to investigate the expression of NUSAP1 in LUAD,the related molecular mechanisms and the relationship with prognosis,and provide scientific basis for the diagnosis,treatment and prognosis prediction of LUAD.Methods:In this study,NUSAP1 expression in LUAD and normal samples was analysed by TCGA and other databases,and the predictive value of NUSAP1 for LUAD diagnosis was revealed by subject operating characteristic(ROC)curves.A chi-square test was used to assess the correlation between NUSAP1 expression and clinical characteristics of LUAD patients.The prognostic value of NUSAP1 in LUAD was determined in the TCGA database using the Kaplan-Meier method,Cox regression analysis,further validated by the GEO database,and a Nomogram column line graph prognostic prediction model was constructed.The NUSAP1-related co-expressed genes were mined through the Linkedomic platform,and the functional enrichment pathways of NUSAP1-related genes were analyzed by GO and KEGG,as well as their potential functions were verified by protein interaction network analysis,while the correlation between NUSAP1 and immune cell infiltration levels and common immune checkpoints was analyzed and explored.Finally,a mi RNA-NUSAP1 regulatory network was constructed by searching for NUSAP1-related upstream regulators through the ENCORI database.Results:NUSAP1 gene and protein level expression were both upregulated in LUAD tissues compared to normal tissues(P < 0.01),and ROC curve analysis revealed an area under the curve AUC of 0.967(95% CI = 0.951-0.983),indicating that NUSAP1 has some diagnostic value for LUAD.NUSAP1 expression was significantly associated with pathological stage,TNM stage,Cox regression analysis showed that high NUSAP1 expression independently predicted poor prognosis in patients with LUAD(P < 0.05).In this study,a Nomogram prognostic prediction model for LUAD patients was constructed based on independent prognostic factors such as NUSAP1 expression,and the results suggested that it was more accurate in predicting survival of LUAD patients.GO and KEGG analyses showed that NUSAP1-related co-expressed genes may play a role in cell cycle regulation,and GSEA functional enrichment analysis was consistent with the results,suggesting that NUSAP1 is involved in cell cycle regulation,multiple tumour-related signalling pathways and immune regulation.Further immune infiltration analysis revealed that NUSAP1 expression levels were significantly negatively correlated with various immune cells(e.g.B cells,NK cells,CD8+ T cells and DC cells)(P < 0.001)and positively correlated with immune checkpoints such as PD-1,PD-L1,LAG3,TIGIT,SIGLEC15,CTLA4 and PD-L2(P < 0.001).Combining the correlation analysis,expression analysis and survival analysis,we concluded that mi R-491-5p may be a potential mi RNA regulator upstream of NUSAP1 in LUAD.Conclusion:NUSAP1 is highly expressed in LUAD tissues and is an independent predictor of poor prognosis in LUAD,and mi R-491-5p may be a potential upstream regulatory molecule of NUSAP1.High NUSAP1 expression is associated with cell cycle regulation,tumor immune escape and multiple signaling pathways,and may be a promising independent prognostic biomarker and potential therapeutic target for LUAD.