Bioinformatics Analysis Of Gene Expression Profile In Clear Cell Renal Cell Carcinoma(ccRCC) And The Study Of The Expression Of ALDH6A1 In CcRCC And Its Significance

Objective: To explore key genes and signaling pathways involved in the progress of clear cell renal cell carcinoma(cc RCC),so as to identify biomarkers and possible therapeutic targets of cc RCC;to verify the differential expression of the key gene ALDH6A1 between cc RCC and normal kidney tissue through immunohistochemistry and analyze its clinical significance.Methods: Four gene expression profiles were integrated and deeply analyzed by R language,from which the differentially expressed genes(DEGs)was screened out.Then DEGs were sorted and clustered based on their functions and signaling pathways through DAVID and KOBAS databases.DEGs-associated protein–protein interaction network(PPI)was performed and visualized through STRING database and Cytoscape software respectively.Then we used MCODE plug-in to select gene functional modules in PPI network.Functions and pathways involved in the modules were also analyzed.Nine key genes were selected from functional modules through Cytohubba plug-in,and we used GEPIA database to verify their differential expression and analyze their prognostic significance.Finally,we compared the expression of the key gene ALDH6A1 in cc RCC to that in normal kidney tissue by immunohistochemistry,statistically analyzed the relationship between the expression level of ALDH6A1 and the clinicopathological features of patients and to evaluate the prognostic value of ALDH6A1 in cc RCC patients.Results: Firstly,333 shared DEGs were identified from the four datasets,involving a total of 32 pathways,among which the most significantly enriched pathway was metabolic pathway.The most significant 3 modules were filtered from PPI and the corresponding genes were found mainly involved in p53 signaling pathway,chemokine signaling pathway and metabolic pathway respectively.Secondly,9 key genes were filtered from the functional modules,among which the m RNA expression levels of key genes FOXM1,CEP55,KIF20 A,SORD and ALDH6A1 were correlated with overall survival(OS)and disease-free survival(DFS)of cc RCC patients.Thirdly,we further confirmed the protein expression level of ALDH6A1 in cc RCC through immunohistochemistry.The results showed that the expression of ALDH6A1 protein in cc RCC tissues was lower than that in normal kidney tissues.In addition,the expression level of ALDH6A1 was correlated with histological grade and clinical stage of cc RCC.Among patients whose pathological grading are G1 or G2,the prognosis is better in patients with high ALDH6A1 m RNA level,and the same trend exists in high grade(G3/G4),early stage(I/II)and advanced stage(?/?)patients.Conclusion: The abnormality of metabolic pathway plays an important role in the process of cc RCC,which needs our attention.The corresponding genes in modules may be of significance in the pathogenesis of cc RCC,providing a reference for us to find new biomarkers and therapeutic targets.Among the key genes,ALDH6A1 is an excellent predictive factor of cc RCC and may play crucial roles in the progression of cc RCC.