关键词:肾肿瘤,预后,计算生物学,SKA1

Abstract:

ObjectiveTo investigate the expression of spindle and kinetochore-associated complex subunit 1 (SKA1) gene in clear cell renal cell carcinoma (ccRCC) and its clinical significance.MethodsThe venous blood samples of 76 preoperative patients with ccRCC and 24 healthy subjects were collected from the Affiliated Tumor Hospital of Xinjiang Medical University from January 2018 to December 2018. The level of SKA1 in whole blood was detected by real-time fluorescence quantitative PCR, and the relationship between SKA1 level and clinicopathological characteristics was analyzed. SKA1 data were retrieved from Oncomine (v4.5), The Human Protein Atlas (THPA) gene databases, The Cancer Genome Atlas (TCGA) databasec (cBioportal) and Gene Expression Omnibus (GEO). The Kaplan-Meier method was used to perform patients' survival analysis based on cBioportal ccRCC data, and the survival rates were compared by log-rank method. The relationship between SKA1 expression level and clinicopathological characteristics was analyzed byχ²test. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of SKA1 mRNA in ccRCC, and enrichment analysis of SKA1 gene was carried out using KOBAS 3.0 online tool.ResultsTwo studies on the expression level of SKA1 mRNA in ccRCC were retrieved from Oncomine (v4.5) database, and there were 38 samples. The results showed that SKA1 mRNA was highly expressed in ccRCC tissues. Further detection showed that the expression level of SKA1 mRNA in ccRCC tissues was significantly higher than that in normal renal tissues [-2.21(-3.56,-1.59)vs.-3.41(-4.55,-1.65)], and there was a statistically significant difference (Z=2.282,P=0.022). The analysis of THPA online website showed that SKA1 protein showed obvious moderate staining in ccRCC tissues, while weakly positive or no expression in normal renal tissues. SKA1 was mainly located in the plasma membrane, which was consistent with the results of mRNA analysis. The results of cBioportal showed that the expression level of SKA1 was significantly correlated with AJCC staging (χ²=21.352,P<0.001), T staging (χ²=19.967,P<0.001), N staging (χ²=11.323, P=0.003) and M staging (χ²=27.248,P<0.001). The relative level of SKA1 in peripheral blood of 76 patients with ccRCC was 0.301±0.147, and 0.162±0.052 in healthy subjects, with a statistically significant difference (t=7.360,P<0.001). The level of SKA1 was correlated with AJCC staging (t=2.445,P=0.017) and lymph node metastasis (t=2.242,P=0.028). The results were consistent with tissue analysis in cBioportal database. Survival analysis showed that in cBioportal database, the expression level of SKA1 mRNA was related to the overall survival rate and disease free survival rate of patients with ccRCC (χ²=22.440, P<0.001; χ²=23.830, P<0.001). In GEO database, the expression level of SKA1 mRNA was not related to the overall survival rate of patients with ccRCC (χ²=0.241,P=0.632). The results of ROC analysis in cBioportal database showed that when the cut-off value was -0.944, the sensitivity and specificity of SKA1 mRNA in the diagnosis of ccRCC were 100% and 98.7%. The area under the ROC curve (AUC) was 0.991 (95%CI: 0.972-1.000). The results of ROC analysis of 76 patients with ccRCC showed that when the cut-off value was 0.235, the sensitivity and specificity of peripheral blood SKA1 in the diagnosis of ccRCC were 75.0% and 95.8%, and the AUC was 0.837 (95%CI: 0.761-0.914). KOBAS enrichment analysis showed that SKA1 high expression samples were enriched in gene sets such as chromosomal centromeres, microtubule polymerization and depolymerization regulation and mitotic spindle check-up points.ConclusionSKA1 is highly expressed in ccRCC tissues, which is obviously related to the prognosis of patients. It can be used as a diagnostic indicator and potential therapeutic target for ccRCC.

Key words:Kidney neoplasms,Prognosis,Computational biology,SKA1