Clinical Significance Of RCC2 In Lung Adenocarcinoma And Its Correlation With Immune Cell Infiltration

BackgroundLung cancer ranked first and second in the incidence of cancer among men and women in China,and is the malignant tumor with the highest incidence and fatality rate.Lung adenocarcinoma is the most common subtype of non-small cell lung cancer(about 40%).In recent years,there is increasing evidence that the tumor microenvironment(TME)characterization plays an important role in mediating late metastasis,immune escape,and resistance to immunotherapy.In molecular biology,the regulator of chromosome condensation 2(RCC2)is known to be a component of the chromosomal passenger complex(CPC).It regulates the assembly of spindle during chromosomal mitosis and cytokinesis,thereby playing a significant role in the development of most tumors.In this study,our main objective was to investigate the clinical significance of RCC2 in the pathogenesis of lung adenocarcinoma(LUAD)and to determine its correlation with immune infiltration.MethodsRCC2 expression was analyzed in pan-cancer using the TIMER database.Tumor Genomic Atlas(TCGA)was used to study the adjacent expression difference,clinical correlation analysis,survival analysis,single and multivariate COX survival analysis of RCC2 in LUAD(lung adenocarcinoma).And we performed immunohistochemistry experiments to verify the differential expression of RCC2 in lung adenocarcinoma and normal tissues,and clinical correlation analysis,survival analysis,multifactor COX analysis.We also analyzed the correlation of RCC2 with 28 tumor-infiltrating immune cells(TIICs)using the TCGA database.Co-expressed genes associated with RCC2 were analyzed with GO enrichment analysis and KEGG enrichment analysis.Using the UALCAN,STRING and GeneMANIA databases,we investigated the protein-coding genes associated with RCC2 and their co-expressed genes in LUAD tissues to predict protein interaction relationships.ResultsAccording to the TIMER database analysis,RCC2 is widely and highly expressed in most carcinomas and also in LUAD.According to the results of the TCGA database,RCC2 mRNA expression was upregulated in LUAD tissues;the survival analysis showed that increased RCC2 expression was associated with decreased survival;the clinical correlation analysis suggested that there was no significant correlation between high RCC2 expression and sex,tumor N stage,tumor T stage,and grade.Multivariate COX survival analysis revealed that patient survival was correlated with RCC2 expression and tumor grade.According to the clinical patient specimens we collected,the results of immunohistochemical staining indicated that RCC2 protein was highly expressed in LUAD compared with normal lung tissue.The survival analysis results suggested that high expression of RCC2 predicted poor survival compared with the low expression group.Multivariate COX survival analysis revealed that RCC2 served as an independent prognostic predictor for LUAD.We associated the expression of RCC2 with clinical information including gender,age,mass size,tumor differentiation,tumor grade,lymph node metastasis,TNM stage,and smoking history,and the results suggested a significant correlation between RCC2 and gender.According to the correlation of RCC2 with 28 tumor-infiltrating immune cells(TIICs)analyzed by the TCGA database,RCC2 is associated with 16 types of TIICs:including activated CD4 T cells,activated DCs,effector membrane CD4 T cells,effector membrane CD8 T cells,etc.Through GO enrichment analysis,we found that RCC2 is associated with chromosome assembly decomposition,DNA recombination,chromatin remodeling,gene silencing in biological processes.Using KEGG enrichment analysis,we found that RCC2 is closely associated with cell cycle,p53 signaling,multiple cancer development,and ubiquitination.ConclusionsOur results demonstrate that RCC2 is highly expressed in LUAD and is associated with prognostic and immune-infiltrating cells.Thus,RCC2 can be considered as a clinically valuable,diagnostic,and prognostic biomarker or a potential therapeutic target for LUAD samples.