To Explore The Expression And Significance Of KNL1 In LUAD

Background and Objectives:Lung cancer is the most common type of cancer among human malignant tumors and remains a leading cause of cancer-related deaths worldwide.According to the results of recent epidemiological surveys,the number of lung cancer cases is increasing year by year,and its mortality rate and incidence rate are second only to breast cancer.Early detection and staging of tumors is very important for the treatment of lung cancer.Non-small cell lung cancer accounts for 80% to 85% of lung cancers,and lung adenocarcinoma is the main subtype.The treatment approach is mainly determined based on the TNM(Tumor,Lymph Node,Metastasis)staging system.Despite the continuous progress in surgical treatment,radiotherapy,chemotherapy,immunotherapy,and targeted therapy,which has greatly improved the survival rate of lung cancer,still 85% of patients eventually die from cancer recurrence or metastasis.In recent years,immune checkpoint inhibitors(ICIs)have been practiced in clinical practice,and immunotherapy for lung cancer has also changed the treatment status of lung cancer.Therefore,there is an urgent need to explore and develop new biomarkers for the early diagnosis,treatment and prognosis of lung adenocarcinoma.KNL1(Kinetochore Scaffold 1)is an important protein that makes up the kinetochore,a multi-subunit protein complex that attaches chromosomes to spindle microtubules to facilitate chromosome separation.KNL1 is regarded as the foundation of kinetochore formation and separation of chromosomes during mitosis,and is involved in various tumor processes such as proliferation and apoptosis.There have been no reports on the research of KNL1 in LUAD and its immune infiltration.In this study,we used bioinformatics technology combined with immunohistochemistry analysis to investigate the expression and clinical significance of KNL1 in LUAD.Methods:We used multiple bioinformatics methods combined with tissue microarray technology.Firstly,we conducted TCGA database mining and analyzed the expression of KNL1 in different types of tumors in the TCGA database using R language.We discussed the association between KNL1 expression and clinical features of lung adenocarcinoma,and evaluated the impact of KNL1 expression on the overall survival of lung adenocarcinoma patients using logistic regression analysis.Secondly,we used immunohistochemistry experiments to validate the overexpression of KNL1 in lung adenocarcinoma and its impact on prognosis.Then,we studied the relationship between KNL1 and immune cells and immune function in lung adenocarcinoma.In addition,we used GO and KEGG enrichment analysis to study the potential biological functions of KNL1 and its differentially expressed genes that we screened.Finally,we studied the relationship between KNL1 expression levels and somatic mutations.Results:The results of bioinformatics analysis showed that KNL1 was highly expressed in lung adenocarcinoma tissues(P<0.001),and the expression of KNL1 was significantly correlated with the gender,smoking history,pathological T stage,FPI,OS,and DSS of lung adenocarcinoma patients(all P<0.05).Kaplan-Meier survival analysis showed that high expression of KNL1 predicted poor prognosis in patients with lung adenocarcinoma(P<0.01),and KNL1 was an independent risk factor for poor prognosis in patients with lung adenocarcinoma(P=0.003).Immunohistochemical experiments showed that the expression of KNL1 in lung adenocarcinoma tissues was significantly higher than that in adjacent tissues(P<0.01),which also verified the bioinformatics analysis.The expression of KNL1 was significantly differentiated from that of activated CD4 T cells with important marker genes,CD8 T cells with effector memory,and memory B cells(P<0.05).Overexpression of KNL1 will produce more cell mutation groups,promote the proliferation of lung adenocarcinoma tumor cells,and produce poor prognosis.Conclusion:In this study,KNL1 was found to be highly expressed in lung adenocarcinoma(LUAD),and its expression level was identified as an independent risk factor for poor prognosis in LUAD patients.We propose that KNL1 may serve as a novel biomarker for the diagnosis and prognosis of LUAD.The expression of KNL1 is associated with immune infiltration and cell mutations,and we suggest that KNL1 is involved in the proliferation of LUAD,providing new insights for targeted immunotherapy in LUAD patients.